Pharmacology - T3 D. Antifungal/antiviral Agents

Front 1

dental anti-fungals are almost always directed at what?
p134

Back 1

infections caused by Candida albicans

Front 2

Nystatin (MYCOSTATIN)
mech, mj. clinical application, mj disadvantage
p134

Back 2

large polyene (antifungal)
1. binds ergosterol in fungi memB and then incorporates pore in memB altering Na, K, and H
2. NOT absorbed orally, ineffective systemic anti-fungal
3. bitter, foul taste (some have sucrose)

Front 3

protocol for Nystatin (NY state) MYCOSTATIN) including suspension and other forms?
p134

Back 3

suspension - 2-3ml swished on ea. side of mouth 5min, then swallow. q6h for 48 hrs after remission
Lozenges - slowly dissolve 2 lozenges q6h (same time as above)

Front 4

Clotrimazone (MYCELEX)
mech, mj. clinical application, mj disadvantage
p134

Back 4

an imidazole antifungal agent. broader spectrum than polyene
1. inhibits ergosterol synthesis (mostly misunderstood)
2. cause hepatitis (rare), better taste,
3. 10 mg troche, q5h/14 days, used with AIDS b/c broader spectrum`

Front 5

Ketoconazole (NIZORAL)
mech, mj. clinical application, mj disadvantage
p135

Back 5

also imidazole.
1. absorbed readily orally, 1st choice when systemic needed, sometimes AIDS
2. significant systemic toxicities. liver monitored close. physician consult, a MUST

Front 6

fluconazole (DIFLUCAN)
mech, mj. clinical application,
p135

Back 6

other "azole"
1. used as a backup systemic antifungal if ketoconazole not working
2. able to combat finger and toenail fungi

Front 7

miconazole (MONISTAT)
clinical application
p 135

Back 7

another "azole"
OTC product mainly used to treat vaginal candidiasis

Front 8

ketoconazole (used systemically) associated with many drug interactions b/c inhibit cytochrome p450 system in liver (CYP3A4) contraindications?

Back 8

warfarin (coumadin) ... anticoagulant
dofetilide (tikosyn) ... antiarrhythmic
"statin" antihyperlipodimic agents
Protease Inhibitors

Front 9

PI (protease inhibitors) - using ketoconazole to treat candida in AIDS pt who also is taking PI, beware, why? do what?
p136

Back 9

consult physician since ketoconazole can cause increase in PI blood levels

Front 10

Acylovir (ZOVIRAX)
mech, mj. normal cell vs. herpes cell
p137

Back 10

antiviral. inhibits DNA poly after bioactivation to acylovir triphosphate
normal: acylovir - cellular thymidine kinase - limited formation of acylovir monophosphate
herpes - a.monophosphat made - cell guanidylte kinase - acylovir triphosphate

Front 11

how do you explain resistance to acylovir (2 mech's)?
p137

Back 11

1. loss of thymidine kinase activity by virus
2. production of thymidine kinase with altered substrate specificity
(host toxicity rare, would need 3000 fold concentration)

Front 12

indications for therapeutic acyclovir?
p137

Back 12

herpes genitalis and mucocutaneous herpes in immunocompromised
2. systemic acylovir can be used phrophalatically to combat herpes in situations where predictable recurrance (ski in sunlight)

Front 13

what is
ganciclovir (FOSCAVIR)
peniclovir (DENAVIR)
famciclovir (FAMVIR)?
p138

Back 13

other agents in acylovir family
ganciclovir (FOSCAVIR) more potent
penciclovir (DENAVIR) less potent, long t1/2
famciclovir (FAMVIR) prodrug for penciclovir

Front 14

Foscarnet (CYTOVENE)
inhibit DNA olymerase through different mech as acylovir family and inhibit reverse transcriptase activity. when is this used?
p138

Back 14

as backup in acylovir resistant HSV infections, administered by IV only. permanent renal damage possible

Front 15

hows retrovirus replicate?
p139

Back 15

virus in cell - loses envelope (Releases RNA & reverse transcriptase) - RNA to DNA - to host - mRNA - proteins (incl. reverse transcriptases) - virus assembled

Front 16

Zidovudine (RETROVIR): azidothymidine, AZT ... first AIDS drug approved by FDA. Mechanism of action?
p139

Back 16

prevents elongation of viral cDNA, after phosphorlation it is incorporated into cDNA by reverse transcriptase of HIV which stops further base addition
2. promotes regeneration of CD+ lymphocytes (somehow)

Front 17

RETROVIR (AZT) resistance (host)?
p139

Back 17

after 6 mo. effectiveness drops, agents can be substituted

Front 18

what do you do if infected with HIV as health care worker?
p139

Back 18

AZT cannot clear HIV from body, used prophylatically to prevent neonatal infection, and 80% effective in preventing conversion in health workers.

Front 19

what drug interaction should one be aware of when taking AZT?
p140

Back 19

acetaminophen - it inhibits the metabolism of AZT, increasing the risk of toxicity (myopathy - weakness)

Front 20

Nevirapine (VIRAMUNE) is the FIRST non-nucleoside reverse transcriptase inhibitor. how does mech. work?
p140

Back 20

binds to the RT and noncompetetively inhibits cDNA synthesis (doesn't act like a base pair)
BUT, rapid resistance development

Front 21

Nevirapine (VIRAMUNE) drug interactions to be aware of are?
p140

Back 21

nevirapine competes with benzodiazepines and macrolide antibiotics for liver enzymes which lead to increased toxicity of these and RT's (contraindication!)

Front 22

HIV protease inhibitors (rasin), what's rasin? mechanism?
p140

Back 22

Ritonavir, Ampirinavir, Saquinivir, Indinavir, Nlfinavir. -> these inhibit actions of HIV-protease, which cleaves enzymes and structural proteins from polypetides generated by viral cDNA

Front 23

HIV protease inhibitors used therapeutically, when?
p140

Back 23

never alone, but used in combination. usually 3 drug treatment with zalcitabine and AZT

Front 24

drug interactions of HIV Protease inhibitors?
p140

Back 24

agents metabolized by CYP3A4 isoenzymes of liver .
CONTRAINDICATED - Benzodiazepines with PI's b/c sever CNS depression b/c decrease in benzodiazepine metabolism