L37 - Drugs Used in Sexually Transmitted Diseases Flashcards
List antibiotics against: cell wall synthesis?
Beta lactams: penicillins, cephalosporins, cephamycins, carbapenems, monobactams
Non-beta lactams: vancomycin, bacitracin
List antibiotics against: cell membrane?
Cell membrane permeability: polymyxins
List antibiotics against: Protein synthesis?
50S subunit: macrolides, linezolid
30S subunit: tetracyclines, aminoglycosides
List antibiotics against: Folate metabolism?
Sulfonamides (inhibits PABA > DHF A)
Trimethoprim (inhibits DHF A > THF A)
List antibiotics against: Nucleic acid synthesis?
DNA: metronidazole, quinolones
RNA polymerase: rifampin
Compare the effects of bacteriostatic and bactericidal antibiotics?
Bacteriostatic (e.g. tetracycline) – inhibits growth of bacteria + rely on immunity, may relapse
Bactericidal (e.g. penicillins) – kills bacteria directly
List narrow and broad spectrum antibiotics?
Narrow = penicillin G, vancomycin
Broad = tetracyclines, amoxillin, augmentin
Give 4 reasons for combination antibiotics?
- Synergistic action for eradication
- Treat mixed bacterial infection
- Overcome resistance
- Reduce toxicity by reducing dose
List 2 diseases caused by Gonococci + one complication?
urethritis (purulent discharge), cervicitis
complication: pelvic inflammatory disease
Treatment regiment for gonococcal infection?
single intramuscular injection of ceftriaxone + single oral dose of azithromycin
** highly effective against penicillin- and tetracycline-resistant strains**
Which antibiotics are no longer effective against gonococcal infections?
Oral cephalosporins (e.g. cefixime) / fluoroquinolones
List 2 diseases caused by Chlamydial infection and outline treatment options? ADR?
urethritis, cervicitis
2 main options***:
Azithromycin (oral)
Doxycycline (oral)
Alternatives:
tetracycline / erythromycin / ofloxacin
ADR: Mild GI disturbance
Treatment option of all stages of syphilis? Treatment for early latent syphilis?
All stages: Penicillin G (IV preferred, oral compliance is low)
Early latent stage:
long-acting preparations (e.g. weekly single IM injection of benzathine penicillin G)
Treatment of STD with multiple pathogens e.g. gonococcal + chlamydial co-infection?
2 options:
1) Single dose of IM ceftriaxone + single dose of oral azithromycin
2) Single dose of IM ceftriaxone + oral doxycycline for 7 days
Causative pathogens of Pelvic inflammatory disease?
Neisseria gonorrhoeae + Chlamydia trachomatis +/- anaerobic bacteria
at Upper female reproductive tract
Describe the route of spread of bacteria causing PID after intercourse with infected male?
Bacteria enter vagina through semen
> > pass through cervix, uterus, fallopian tube, ovaries
> > exit to peritoneal cavity
Inpatient* treatment option for pelvic inflammatory disease?
broad spectrum antimicrobial coverage:
1) IV cefoxitin / cefotetan (= cephamycins) + oral doxycycline (tetracycline)
2) IV clindamycin (inhibits 50S) + aminoglycoside (e.g. streptomycin)
Outpatient treatment option for pelvic inflammatory disease?
single IM dose of ceftriaxone + oral doxycycline ± metronidazole
List 3 vaginal infections?
Bacterial vaginosis
Trichomoniasis
Vulvovaginal candidiasis
Treatment for Bacterial vaginosis?
3 options:
1) oral metronidazole
2) Metronidazole gel applied intravaginally
3) Clindamycin (oral / intravaginal)
Treatment for Trichomoniasis? *caused by Trichomonas vaginalis *
Single dose metronizadole or Tinidazole
anti-bacterial, anti-parasitic
Treatment for vulvovaginal candidiasis?
Topical azole antifungal agents against Candida:
1) Intravaginal use: clotrimazole, miconazole
2) Oral fluconazole
3) AmB deoxycholate and flucytosine for resistant strains
List antifungal agents that alter cell membrane permeability?
Target cell membrane: Azoles, Polyenes, Terbinafine
Target cell wall: Echinocandins
List antifungal agents that alter DNA synthesis?
Flucytosine
List antifungal agents that alter Microtubule structures?
griseofulvin
Treatment options for uncomplicated genital herpes?
1) Acyclovir (oral)
2) Valacyclovir
3) Famciclovir
2,3 are acyclovir derivatives with higher bioavailability
Causative pathogen of Genital warts and treatment options?
human papillomavirus (HPV)
1) imiquimod cream (= immune response modifier)
2) Podofilox solution / gel (aka podophyllotoxin = antimitotic drug)
3) Sinecatechins ointment
Recurred warts:
local intra-lesional alfa interferon
Treatment for complicated/ severe genital herpes?
foscarnet and cidofovir
IV acyclovir
MoA of acyclovir?
= acyclic guanosine derivative, inhibits viral DNA synthesis
- Selectively activated in infected cells by viral-specific thymidine kinase + cellular kinases
- Competitive inhibition of viral DNA polymerase with deoxyguanosine triphosphate (dGTP)
- Incorporate dGTP into viral DNA (primer strand)»_space; chain terminal
Compare the indication of acyclovir based on diff. preparations?
IV = serious HSV infection (can use foscarnet, cidofovir) Oral = treat primary infections
(Topical = ineffective)
Compare the activation of Valacyclovir and Famiciclovir?
Valacyclovir = Ester of ACV»_space; converted to ACV
Famiciclovir = metabolized to the active penciclovir, same MoA as ACV
Describe how retroviruses incorporate its genetic material into host?
uses own reverse transcriptase*
|»_space; DNA incorporated into host DNA by integrase*
Explain why antiretroviral therapy (ART) is multi-drug combo?
- Maximize inhibition of viral replciaiton
- Minimize drug toxicities
- Different targets in viral mechanism = lower resistance
List 5 categories of antiretroviral drugs?
- Entry inhibitors
- NRTI and NNRTIs
- Integrase inhibitor
- Protease inhibitor
- integrase strand transfer inhibitors (INSTI)
Outline the typical regimen for HIV infection?
1) 2 NRTI + INSTI/NNRTI/PI
2) dolutegravir (PI, DTG) + lamivudine (NRTI: 3TC)
4 primary goals of ART for HIV infection?
Reduce HIV-associated morbidity and mortality
preserve immunologic function: increase CD4 T cells, decrease opportunistic infections
suppress plasma HIV viral load
prevent HIV transmission
Name 2 NRTIs and give MoA?
zidovudine (AZT) and lamivudine (3TC)
1) bioactivation by cellular kinases into triphosphate form
2) Compete with native nucleotides to inhibit HIV reverse transcriptase
3) Incorporate into viral DNA for chain termination
Admin, PK and ADR of NRTIs?
Oral
well absorbed and well distributed (t1/2 = 1h)
anemia and neutropenia
Lipodystrophy, Lactic acidosis, hepatic steatosis
Name one NtRTI and give one advantgae over NRTI?
Tenofovir (TDF) = nucleotide analogue (NtRTI) = nucleoside + 1 phosphate group
Faster action: no need to be activated by enzyme
Name 3 Non-NRTIs /NNRTI?
Non-nucleoside reverse transcriptase inhibitors:
nevirapine (NVP), efavirenz (EFV), delavirdine (DLV)
MoA of NNRTIs?
Bind non-competitively and reversibly to directly inhibit the HIV-1 reverse transcriptase
ADR of NNRTIs?
General:
- Rash
- D/D interaction
Efavirenz = Neuropsychiatric
Nevirapine* = hepatotoxicity, Rash
Name 3 protease inhibitors?
saquinavir (prototype)
ritonavir**, lopinavir
** Used as a booster of bioavailability of other PI**
All oral intake
MoA of protease inhibitors?
Specifically inhibit HIV-1 protease
> > cannot produce mature infectious virions
ADR of Protease inhibitors?
Rapid emergence of resistance
D/D interactions (CYP450)
GI disturbances
Lipodystrophy, Hyperlipidemia, Insulin resistance, diabetes
Name 3 INSTI, MoA, ADR?
Integrase Strand Transfer Inhibitors (INSTI): Raltegravir**, dolutegravir & elvitegravir
Inhibits catalytic activity of HIV-1 integrase
» prevents propagation of the viral infection into host CD4 cells
» prevent HIV replication
Low ADR = preferred
Name 2 viral entry inhibitors?
Maraviroc
Enfuviritide
MoA of Enfuvirtide?
Fusion inhibitor
inhibits the fusion of the viral transmembrane glycoprotein gp41 with the host cell (CD4) surface
MoA of Maraviroc?
antagonist of the CCR5 chemokine co-receptor on CD-4 T-cells
> > prevents interaction between HIV gp120 and the CCR5 protein
> > prevent HIV fusion
Which class of ART cause lactic acidosis and hepatic steatosis?
all NRTI
Which class of ART cause Hyperlipidemia, insulin resistance and diabetes?
All PI
Which class of ART cause rash?
All NNRTI, especially Nevirapine
Which class of ART cause increased bleeding in hemophiliacs?
All PI
