Transcript Lecture 8- treatment of sexually transmited diseases

DRUGS USED FOR THE
TREATMENT OF SYPHILIS
& GONORRHEA
PROF.
AZZA
El-Medany
OBJECTIVES
At the end of lecture , the
students should able to :
 List The drugs used in the
treatment of syphilis
List the drugs used in
treatment of gonorrhea.
 Describe The mechanism of
action, adverse effects of &
clinical indication of each
drug

OBJECTIVES ( continue)



Describe the contraindications
of each drug used
Describe the recommended
regimens used for treatment of
syphilis & gonorrhoea
Describe the alternative
treatments in allergic patients to
certain antibiotics
Epidemiology
Syphilis Definition

Sexually acquired infection

Etiologic agent: Treponema
pallidum

Disease progresses in stages

May become chronic without
treatment
6
Pathogenesis
Treponema pallidum
Electron photomicrograph, 36,000 x.
Source: CDC/NCHSTP/Division of STD Prevention, STD Clinical Slides
7
Classification Of Syphilis

A primary stage ( a single
sore ( a chancre ) )
Secondary Stage

Skin rash & mucous
membranes lesions
Clinical Manifestations
Secondary Syphilis:
Palmar/Plantar Rash
Source: Seattle STD/HIV Prevention
Training Center at the University of
Washington, UW HSCER Slide Bank
Source: CDC/NCHSTP/Division of STD
Prevention, STD Clinical Slides
10
Clinical Manifestations
Tertiary (Late) Syphilis

Approximately 30% of untreated
patients progress to the tertiary
stage within 1 to 20 years

Rare because of the widespread
use of antibiotics

Manifestations

Cardiovascular syphilis
11
Latent stage
70% may have NO SYMPTOMS
Congenital Syphilis

If a woman is pregnant and has
symptomatic or asymptomatic
early syphilis, hematogenously
disseminating organisms may
pass through the placenta to
infect the fetus.
Clinical Manifestations
Congenital Syphilis Perforation of Palate
14
Source: CDC/ NCHSTP/ Division of STD Prevention, STD Clinical Slides
Neurosyphilis - Spirochetes in Neural
Tissue
Silver stain, 950x
15
Source: CDC/ NCHSTP/ Division of STD Prevention, STD Clinical Slides
Therapy of syphilis
Penicillins (β-lactam
antibiotic
PENICILLINS

Bactericidal Drugs

Mechanism of action
Inhibit the synthesis of
bacterial cell wall .
Preparations of penicillins used
for treatment of syphilis
Penicillin G (IV )
 Procaine penicillin (IM )
 Benzathine penicillin (IM )

Penicillin G

Short duration of action
( 4-6 hrs)

Acid unstable

Penicillinase sensitive
Procaine penicillin

Long acting (24-48hrs)

Acid unstable

Penicillinase sensitive
Benzathine penicillin

Long acting
( every 3-4 weeks)

Acid unstable

Penicillinase sensitive
Adverse effects of
penicillins
Hypersensitivity
 Nephritis
 Convulsions with high
doses or in renal failure

Therapy for Primary, Secondary, and
Early Latent Syphilis


Benzathine penicillin 2.4 million units IM in a
single dose
I
24
For Allergic Patients To Penicillins

Tetracyclines such as:
Doxycycline
Tetracycline

Macrolides such as:
Azithromycin

Cephalosprins such as :
Ceftriaxone
cefixime
TETRACYCLINES

Doxycycline

Well absorbed orally
Long-acting

Tetracycline

Absorption after oral
administration ( 60-70%)

Given every 6hrs.
Mechanism of action

Bacteriostatic

Inhibit bacterial protein
synthesis by reversibly
binding to 30 S bacterial
ribosomal subunits .
Tetracyclines in treatment of
syphilis
Doxycycline
100 mg orally twice daily for 14
days

Tetracycline 500 mg
orally 4 times daily
for 14 days
Side effects:
1-gastric upset( nausea,
vomiting, diarrhea)
Side Effects
and
contraindication
2-Effects
on
calcified
tissues (discoloration
of
teeth)&bone
deformity
3-Hepatotoxicity
4-Phototoxicity
5-vestibular
problems
(vertigo,nausea,
vomiting)
6-Superinfections
Contraindication:
1. Children ( below 10 years)
2. Pregnancy---------3- Nursing mothers
MACROLIDES
(Azithromycin)
Mechanism of action

Inhibits bacterial protein
synthesis by binding to
bacterial 50S ribosomal
subunits
Pharmacokinetics






Acid stable
Penetrates into most tissues
except CSF
T1/2 2-4 days
Once daily dose
Should given 1hour before or 2
hours after meals
Does not inactivate cytochrome
P450
ADVERSE EFFECTS
.

Gastric upset
Indication in syphilis

2g single dose is effective in
treatment of early syphilis
Cephalosporinsns
β-lactam antibiotics
Mechanism of action
3rd Generation
cephalosporins
Inhibits bacterial cell wall
synthesis
e.g. cefixime
Bactericidal
e.g. Ceftriaxone
Adverse effects

Allergic manifestations

Thrombophilibitis

Superinfection

Diarrhea
Therapy for Neurosyphilis

Aqueous crystalline penicillin G 18-24 million units
per day, administered as 3-4 million units IV every
4 hours or continuous infusion for 10-14 days IV

Alternative regimen (if compliance can be
ensured):

Procaine penicillin 2.4 million units IM once daily PLUS
Probenecid 500 mg orally 4 times a day, both for 10-14
days
Therapy for Neurosyphilis

Aqueous crystalline penicillin G 18-24 million units
per day, administered as 3-4 million units IV every
4 hours or continuous infusion for 10-14 days IV

Alternative regimen (if compliance can be
ensured):

Procaine penicillin 2.4 million units IM once daily PLUS
Probenecid 500 mg orally 4 times a day, both for 10-14
days
Therapy for Syphilis in
Pregnancy



Treat with penicillin according to
stage of infection.
Erythromycin is no longer an
acceptable alternative drug in
penicillin-allergic patients.
Patients who are skin-testreactive to penicillin should be
desensitized in the hospital and
treated with penicillin.
GONORRHEA
Caused by Neisseria gonorrhea, a pus producing bacteria
Up to 1 MILLION people affected each year
Teenagers (15-19) have the highest rate if infection
GONORRHEA
60% of Females DON’T KNOW they have it.
NO
YMPTOM
S
20% - 40% of Males DON’T KNOW they have it.
NO
YMPTOM
S
BUT: Does spread to partners
Does damage the body
: Recommended regimens
( 1st line treatment)
Uncomplicated gonorrheal infections
Single –dose treatment with 3rd
generation cephalosporins
 500

mg of ceftriaxone, IM
500mg of Cefotaxime IMI
Macrolides



Azithromycin as a single oral
dose 1 g.in combination with
ceftriaxone 250 mg IMI
Or high dose 2g. As a single
oral dose
In pregnant & breast feeding
mothers azithromycin is given
as a single oral dose 1g
FLUOROQUINOLONES
Single oral dose of :
Ciprofloxacin 500 mg orally
Ofloxacin 400 mg orally
Levofloxacin
MECHANISM OF ACTION of
fluoroquinolones

All are bactericidal

Inhibit DNA synthesis by
inhibiting DNA gyrase enzyme
ADVERSE EFFECTS
GIT upset
Diarrhea
nausea
arthropathy
headache
phototoxicity
dizziness
CONTRAINDICATIONS

Pregnancy

Nursing mothers

Adolescent under 18 years
Alternative treatment in allergic
patients to 1st line treatment
Spectinomycin

2g IMI
( once )
Mechanism of action

Inhibits protein synthesis
by binding to 30 S
ribosomal subunits
Adverse Effects
1. Pain at the
site of
injection
2. Fever
Nausea
Nephrotoxicity
(not common)
CONTINUE
Complicated gonorrheal
infections
Spread through blood stream
 EYE



Joints
Heart valves
Brain
Antibiotics that are no
longer recommended
for gonorrhea
treatment
Continue




Sulfonamides
Penicillins
Tetracyclines
Oral cephalosporins
Harmful effects of gonorrhea
Newborn eye infections, may lead to
blindness
Adult eye infections, spread on
fingers, can lead to blindness
Treatment of Complicated
gonorrheal infections
With conjunctivitis in new
born
 Silver
nitrate
Its germicidal effects are
due to precipitation of
bacterial proteins by
liberated silver ions
Silver nitrate ( continue)

Put into conjunctival sac
once immediately after
birth ( not later 1 h after
birth )
ERYTHROMYCIN

0.5% ointment for treatment
& prevention of corneal &
conjunctival infections.

Put into conjunctival sac
immediately after birth ( no
later 1 hr after delivery )