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342 > Current & Advanced Treatments for Sexually Transmitted Bacterial Infections > Flashcards

Current & Advanced Treatments for Sexually Transmitted Bacterial Infections Flashcards

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1
Q

one of the most common sexually transmitted infections (STIs)

A

chlamydia

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2
Q

what species of bacteria are linked to chlamydia that mainly infect humans

A

chlamydiae -
chlamydia trachomatis
chlamydia pneumonia

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3
Q

symptoms of chlamydia (4)

A

(can have no symptoms)

pain when urinating

unusual discharge from vagina, penis, rectum

in females, pain in abdomen, bleeding after sex, bleeding between periods

in males, pain and swelling in testicles

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4
Q

causes of chlamydia (2)

A

unprotected vaginal, anal, oral sex
infected semen or vaginal fluid getting into eye

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5
Q

complications of chlamydia in females (2)

A

infection can spread to womb, ovaries, fallopian tubes
increased risks of cervical cancer

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6
Q

what condition can chlamydia cause in females if left untreated

A

pelvic inflammatory disease (PID)

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7
Q

symptoms of pelvic inflammatory disease (PID) (3)

A

infertility

increased risk of ectopic pregnancy

if untreated during pregnancy, can cause premature labour

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8
Q

complications of chlamydia in males (2)

A

can cause epididymitis
can cause epididymo-orchitis

(both can affect fertility)

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9
Q

what are the first line treatments of chlamydia (2)

A

azithromycin

doxycycline

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10
Q

what is the dose/ duration of azithromycin

A

single dose

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11
Q

what is the dose/ duration of doxycycline

A

7 day course

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12
Q

between azithromycin and doxycycline, which is prescribed first?

A

initially azithromycin and then doxycycline if needed, but due to resistance other way around since 2019

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13
Q

what is azithromycin classed as

A

macrolide antibiotic

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14
Q

what is azithromycin a derivitave of

A

semi synthetic derivative of erythromycin

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15
Q

what is epididymitis

A

inflammation of epididymis

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16
Q

what is epididymo-orchitis

A

inflammation of epididymis and testicles

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17
Q

is azithromycin delivered at a high or low concentration

A

high concentration

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18
Q

how is azithromycin administered

A

intramuscular injection at site of infection

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19
Q

why is azithromycin administered as an intramuscular injection at site of infection

A

to ensure tissue concentration is high but plasma concentration is low - highest bioavaliability

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20
Q

what other infections are azithromycin used for

A

respiratory, urogenital, dermal and other bacterial infections

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21
Q

mechanism of action of azithromycin

A

binds at polypeptide exit tunnel of 50S subunit of bacterial ribosome

inhibits mRNA translation thus

inhibits bacterial protein synthesis

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22
Q

is azithromycin bacteriostatic or bacteriocidal

A

bacteriostatic

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23
Q

what is meant by bacteriostatic

A

stops bacteria from reproducing, but doesn’t kill them

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24
Q

what are the two mechanisms of azithromycin resistance

A

alteration of ribosomal components via methylation aka changes antibiotic target and prevents antibiotic binding to it

upregulation of drug efflux pump activity, therefore decreasing intra-bacterial accumulation aka pushing drug out

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25
one mechanism of azithromycin resistance is alteration of ______ components via methylation
ribosomal
26
one mechanism of azithromycin resistance is alteration of ribosomal components via ____
methylation
27
one mechanism of azithromycin resistance is ____ drug efflux pump activity, therefore decreasing intra-bacterial accumulation
increased
28
one mechanism of azithromycin resistance is increased drug efflux pump activity, therefore ______ intra-bacterial accumulation
decreasing
29
one mechanism of azithromycin resistance is increased drug efflux pump activity, therefore decreasing _________ _____
intrabacterial accumulation
30
in azithromycin resistance, what efflux pump contributes
Mef transporter
31
doxycycline's mechanism of action is ____ to azithromycin
similar
32
what is doxycycline's mechanism of action
inhibits protein production by binding the 30S subunit (same as azithromycin but different subunit)
33
is doxycycline bacteriostatic or bacterocidal
bacteriostatic
34
what are the two mechanisms of doxycycline resistance
increased expression of efflux pumps increased expression of ribosomal protection proteins e.g. via methylating ribosomal subunits
35
how are we infected by chlamydia
chlamydia bind to receptors on membrane undergo endocytosis internalise and replicate burst from cell and infect new cells
36
what is the interaction between chlamydia and receptor binding
chlamydia binds to platelet derived growth factor receptor-β (PDGFR-β), a RTK (new preventative medications working towards temporarily inhibiting cells from making PDGFR-β to prevent interaction with chlamydia and spread of infection)
37
what is growth factor receptor-β (PDGFR-β)
a RTK - receptor tyrosine kinase
38
new medications working towards temporarily inhibiting cells from making PDGFR-β to prevent spread of infection. what method does this use
gene therapy
39
what does gene therapy in treating chlamydia rely on
small interfering RNA (siRNA)
40
what does siRNA do
promote recruitment of RISC
41
what does recruitment of RISC from siRNA cause
degradation of mRNA preventing protein synthesis aka cells will not produce PDGFR-β and chlamydia cannot bind to these receptors, cannot enter cell
42
how can the uptake of siRNA be facilitated
using nanoparticles inc bioavailability, inc sustained drug release, enhances barrier penetration
43
what other role do siPDGFR-β nanoparticles play in already infected cells (chlamydia)
trigger autophagy cascade by upregulating autophagy, including of bacteria
44
what is autophagy
the regulated mechanism of the cell that removes unnecessary or dysfunctional components degrades invading pathogen
45
what bacteria is gonorrhoea caused by
Neisseria gonorrhoeae or gonococcus
46
how else can gonorrhoea be indirectly spread
can be passed from a mother to her baby during childbirth
47
symptoms of gonorrhoea (4)
pain when urinating unusual discharge from vagina, penis, rectum in females, pain in abdomen, bleeding after sex, bleeding between periods in males, swelling of foreskin, pain, swelling in testicles
48
how is gonorrhoea spread
unprotected vaginal, anal, oral sex
49
first line treatment of gonorrhoea
oral azithromycin and intramuscular ceftraxione
50
the first line treatment of gonorrhoea is oral azithromycin and intramuscular ceftraxione. how much is administered
single dose of both antibacterial agents
51
what type of drug is ceftraxione classed as
belongs to the β-lactam family of antibiotics
52
ceftriaxone mechanism of action (5)
binds to and inhibits transpeptidases these catalyse cross linking of peptidoglycan polymers which form bacterial cell wall prevents final linking stage of cell wall synthesis, leading to weakened cell wall with gaps water can enter bacterial cells cells swell and lyse due to osmotic pressure within cell - burst
53
is ceftriaxone bacteriostatic or bactericidal
bactericidal
54
ceftriaxone mechanism of resistance (2)
mutation of transpeptidases e.g. of target site preventing binding increased drug efflux pump activity and decreased drug influx pumps
55
what medication has been developed in response to antibiotic resistant gonorrhoea
zoliflodacin
56
what does zoliflodacin in the treatment of gonorrhoea target
bacterial type 2 topoisomerases
57
zoliflodacin mechanism of action (6)
topoisomerase II e.g. DNA gyrase causes double strand break, and then religates the strands back together to relive tension and prevent snaps from supercoiling supercoiling can cause DNA to break, triggers apoptosis zoliflodacin stabilises topoisomerase 2 in a conformation - by inhibiting ATP-dependent conformational changes and ATPase activity, preventing it from ligating DNA back together causing accumulation of double strand DNA breaks triggers bacterial cell death
58
is zoliflodacin bacteriostatic or bactericidal
bactericidal
59
Zoliflodacin shows ____ efficacy for human Topo II enzymes to date
little ideal as does not affect human cells, just bacterial
60
what else can zoliflodacin be used for
antibiotic resistant chlamydia as well as gonorrhoea
61
what bacteria is syphilis caused by
treponema pallidum
62
symptoms of syphilis (5)
small painless sores or ulcers on penis, vagina, anus, mouth blotchy red rash that affects palms of hands or soles of feet small skin growths like warts that can develop in women on vulva or in both men and woman around anus white patches in mouth tiredness, headaches, joint pains, fever, swollen glands in neck, groin, armpits
63
if left untreated, what can syphilis cause
neurosyphilis
64
what population is neurosyphilis most often found in
in HIV-positive patients as they are immunocompromised
65
first line treatment of syphilis (3)
doxycycline erythromycin (works same as azithromycin, but poorer ADME) benzathin penicillin
66
how is benzathin penicillin administered
single intramuscular injection
67
how long is doxycycline and erythromycin recommended for
14 days
68
zoliflodacin is more effective in treating ___/___ infection than ____
urogenital/rectal pharyngeal as poor drug penetration into pharyngeal tissue
69
chlamydiae trachomitis primarily targets ___ cells
gential epithelial
70
siRNA is administered ____
topically
71
PLGA
commonly used polymer for intravaginal nanoparticle formulations, is biodegradeable and naturally degrades into lactic acid and glycolytic acid through hydrolysis in body where can join cellular process or be excreted unchanged but, hydrophobic, less able to penetrate mucus
72
new advancements
PLGA zoliflodacin siRNA viral treatments - tenofovir gel
73
tenofovir gel case study
usually for HIV - viral CAPRISA 004 trial found 1% tenofovir gel had some broad spectrum antimicrobial ability against bacterial STIs led to in vitro studies that tenofovir exhibit some activity against bacterial pahtogens like chlamydia trachomitis not studied enough yet
74
complications for babies born to mothers infected with syphilis
severe, including death and loss of vision and hearing
75
clinical shit we gaf about - 3
syphilis - treponemia pallidium (can cause neurosyphilis) chlamydia (which can lead to PID, epididymis, mo orchitis - all affect fertility) gonorrhoea
76
current/ old treatments - 7
syphilis - doxyxyxline, ezithromycin, benzathin penicillin chlamydia - azithromycin, doxyxyxline gonorrhoea - oral azithromycin and intramuscular ceftraxione
77
new treatments - 5
syphilis - tenofovir gel case study chlamydia - zoliflodacin, Cas9 gene therapy and nanoparticles (like PLGA) gonorrhoea - zoliflodacin

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