L37 - Drugs Used in Sexually Transmitted Diseases

Question 1

List antibiotics against: cell wall synthesis?

Answer 1

 Beta lactams: penicillins, cephalosporins, cephamycins, carbapenems, monobactams

 Non-beta lactams: vancomycin, bacitracin

Question 2

List antibiotics against: cell membrane?

Answer 2

Cell membrane permeability: polymyxins

Question 3

List antibiotics against: Protein synthesis?

Answer 3

 50S subunit: macrolides, linezolid

 30S subunit: tetracyclines, aminoglycosides

Question 4

List antibiotics against: Folate metabolism?

Answer 4

 Sulfonamides (inhibits PABA > DHF A)

 Trimethoprim (inhibits DHF A > THF A)

Question 5

List antibiotics against: Nucleic acid synthesis?

Answer 5

 DNA: metronidazole, quinolones

 RNA polymerase: rifampin

Question 6

Compare the effects of bacteriostatic and bactericidal antibiotics?

Answer 6

Bacteriostatic (e.g. tetracycline) – inhibits growth of bacteria + rely on immunity, may relapse

Bactericidal (e.g. penicillins) – kills bacteria directly

Question 7

List narrow and broad spectrum antibiotics?

Answer 7

Narrow = penicillin G, vancomycin

Broad = tetracyclines, amoxillin, augmentin

Question 8

Give 4 reasons for combination antibiotics?

Answer 8

• Synergistic action for eradication
• Treat mixed bacterial infection
• Overcome resistance
• Reduce toxicity by reducing dose

Question 9

List 2 diseases caused by Gonococci + one complication?

Answer 9

urethritis (purulent discharge), cervicitis

complication: pelvic inflammatory disease

Question 10

Treatment regiment for gonococcal infection?

Answer 10

single intramuscular injection of ceftriaxone + single oral dose of azithromycin

** highly effective against penicillin- and tetracycline-resistant strains**

Question 11

Which antibiotics are no longer effective against gonococcal infections?

Answer 11

Oral cephalosporins (e.g. cefixime) / fluoroquinolones

Question 12

List 2 diseases caused by Chlamydial infection and outline treatment options? ADR?

Answer 12

urethritis, cervicitis

2 main options***:
 Azithromycin (oral)
 Doxycycline (oral)

Alternatives:
tetracycline / erythromycin / ofloxacin

ADR: Mild GI disturbance

Question 13

Treatment option of all stages of syphilis? Treatment for early latent syphilis?

Answer 13

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)

Question 14

Treatment of STD with multiple pathogens e.g. gonococcal + chlamydial co-infection?

Answer 14

2 options:

1) Single dose of IM ceftriaxone + single dose of oral azithromycin
2) Single dose of IM ceftriaxone + oral doxycycline for 7 days

Question 15

Causative pathogens of Pelvic inflammatory disease?

Answer 15

Neisseria gonorrhoeae + Chlamydia trachomatis +/- anaerobic bacteria

at Upper female reproductive tract

Question 16

Describe the route of spread of bacteria causing PID after intercourse with infected male?

Answer 16

Bacteria enter vagina through semen

> > pass through cervix, uterus, fallopian tube, ovaries

> > exit to peritoneal cavity

Question 17

Inpatient* treatment option for pelvic inflammatory disease?

Answer 17

broad spectrum antimicrobial coverage:

1) IV cefoxitin / cefotetan (= cephamycins) + oral doxycycline (tetracycline)
2) IV clindamycin (inhibits 50S) + aminoglycoside (e.g. streptomycin)

Question 18

Outpatient treatment option for pelvic inflammatory disease?

Answer 18

single IM dose of ceftriaxone + oral doxycycline ± metronidazole

Question 19

List 3 vaginal infections?

Answer 19

Bacterial vaginosis

Trichomoniasis

Vulvovaginal candidiasis

Question 20

Treatment for Bacterial vaginosis?

Answer 20

3 options:

1) oral metronidazole
2) Metronidazole gel applied intravaginally
3) Clindamycin (oral / intravaginal)

Question 21

Treatment for Trichomoniasis? *caused by Trichomonas vaginalis *

Answer 21

Single dose metronizadole or Tinidazole

anti-bacterial, anti-parasitic

Question 22

Treatment for vulvovaginal candidiasis?

Answer 22

Topical azole antifungal agents against Candida:

1) Intravaginal use: clotrimazole, miconazole
2) Oral fluconazole
3) AmB deoxycholate and flucytosine for resistant strains

Question 23

List antifungal agents that alter cell membrane permeability?

Answer 23

Target cell membrane: Azoles, Polyenes, Terbinafine

Target cell wall: Echinocandins

Question 24

List antifungal agents that alter DNA synthesis?

Answer 24

Flucytosine

Question 25

List antifungal agents that alter Microtubule structures?

Answer 25

griseofulvin

Question 26

Treatment options for uncomplicated genital herpes?

Answer 26

1) Acyclovir (oral) 2) Valacyclovir 3) Famciclovir 2,3 are acyclovir derivatives with higher bioavailability

Question 27

Causative pathogen of Genital warts and treatment options?

Answer 27

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

Question 28

Treatment for complicated/ severe genital herpes?

Answer 28

foscarnet and cidofovir IV acyclovir

Question 29

MoA of acyclovir?

Answer 29

= 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) >> chain terminal

Question 30

Compare the indication of acyclovir based on diff. preparations?

Answer 30

``` IV = serious HSV infection (can use foscarnet, cidofovir) Oral = treat primary infections ``` (Topical = ineffective)

Question 31

Compare the activation of Valacyclovir and Famiciclovir?

Answer 31

Valacyclovir = Ester of ACV >> converted to ACV Famiciclovir = metabolized to the active penciclovir, same MoA as ACV

Question 32

Describe how retroviruses incorporate its genetic material into host?

Answer 32

uses own reverse transcriptase* | >> DNA incorporated into host DNA by integrase*

Question 33

Explain why antiretroviral therapy (ART) is multi-drug combo?

Answer 33

- Maximize inhibition of viral replciaiton - Minimize drug toxicities - Different targets in viral mechanism = lower resistance

Question 34

List 5 categories of antiretroviral drugs?

Answer 34

- Entry inhibitors - NRTI and NNRTIs - Integrase inhibitor - Protease inhibitor - integrase strand transfer inhibitors (INSTI)

Question 35

Outline the typical regimen for HIV infection?

Answer 35

1) 2 NRTI + INSTI/NNRTI/PI | 2) dolutegravir (PI, DTG) + lamivudine (NRTI: 3TC)

Question 36

4 primary goals of ART for HIV infection?

Answer 36

Reduce HIV-associated morbidity and mortality preserve immunologic function: increase CD4 T cells, decrease opportunistic infections suppress plasma HIV viral load prevent HIV transmission

Question 37

Name 2 NRTIs and give MoA?

Answer 37

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

Question 38

Admin, PK and ADR of NRTIs?

Answer 38

Oral well absorbed and well distributed (t1/2 = 1h) anemia and neutropenia Lipodystrophy, Lactic acidosis, hepatic steatosis

Question 39

Name one NtRTI and give one advantgae over NRTI?

Answer 39

Tenofovir (TDF) = nucleotide analogue (NtRTI) = nucleoside + 1 phosphate group Faster action: no need to be activated by enzyme

Question 40

Name 3 Non-NRTIs /NNRTI?

Answer 40

Non-nucleoside reverse transcriptase inhibitors: nevirapine (NVP), efavirenz (EFV), delavirdine (DLV)

Question 41

MoA of NNRTIs?

Answer 41

Bind non-competitively and reversibly to directly inhibit the HIV-1 reverse transcriptase

Question 42

ADR of NNRTIs?

Answer 42

General: - Rash - D/D interaction Efavirenz = Neuropsychiatric Nevirapine* = hepatotoxicity, Rash

Question 43

Name 3 protease inhibitors?

Answer 43

saquinavir (prototype) ritonavir**, lopinavir ** Used as a booster of bioavailability of other PI** All oral intake

Question 44

MoA of protease inhibitors?

Answer 44

Specifically inhibit HIV-1 protease >> cannot produce mature infectious virions

Question 45

ADR of Protease inhibitors?

Answer 45

Rapid emergence of resistance D/D interactions (CYP450) GI disturbances Lipodystrophy, Hyperlipidemia, Insulin resistance, diabetes

Question 46

Name 3 INSTI, MoA, ADR?

Answer 46

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

Question 47

Name 2 viral entry inhibitors?

Answer 47

Maraviroc | Enfuviritide

Question 48

MoA of Enfuvirtide?

Answer 48

Fusion inhibitor inhibits the fusion of the viral transmembrane glycoprotein gp41 with the host cell (CD4) surface

Question 49

MoA of Maraviroc?

Answer 49

antagonist of the CCR5 chemokine co-receptor on CD-4 T-cells >> prevents interaction between HIV gp120 and the CCR5 protein >> prevent HIV fusion

Question 50

Which class of ART cause lactic acidosis and hepatic steatosis?

Answer 50

all NRTI

Question 51

Which class of ART cause Hyperlipidemia, insulin resistance and diabetes?

Answer 51

All PI

Question 52

Which class of ART cause rash?

Answer 52

All NNRTI, especially Nevirapine

Question 53

Which class of ART cause increased bleeding in hemophiliacs?

Answer 53

All PI