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Drug Therapy Of
Syphilis
Labeeb
102
Sexually Transmitted Diseases ( STD )
• Syphilis
• Gonorrhea
• Non Gonococcal
Urethritis
• Chancroid
• Lymphogranuloma
Venereum
• Granuloma Inguinale
• Vaginitis
• Genital Warts
• Genital Herpes
• AIDS
• Hepatitis B
Syphilis
• Chronic venereal infection caused by the spirochete
Treponema pallidum.
• Source of infection : active cutaneous or mucosal
lesion in a sexual partner in early stages of syphilis.
Classification
Stage Acquired Congenital
Early Primary
Secondary
Latent
Late Latent
Benign Tertiary
Cardiovascular
Neurosyphilis
• Penicillin is the drug of choice for all stages of infection.
Acquired syphilis :
Primary syphilis :
• IP – between 14 & 28 days.
• A dull red macule → papular → indurated ulcer – Hard
Chancre.
• Inguinal lymph nodes enlarged, mobile, discrete & rubbery.
• Chancre and lymph nodes : painless.
• Without treatment, resolves within 2-6 weeks to leave thin
atrophic scar.
• Extra genital chancres – fingers, tongue, tonsil, nipple, anus.
• Diagnosed by Dark field microscopy or direct Fluorescent Ab
tests of exudates.
Oral chancre Hard Chancre
Secondary syphilis :
• 6-8 weeks after development of chancre when treponemes
disseminate.
• Mucocutaneous lesions & generalised lymphadenopathy.
• Fever, malaise, headache common.
• Rashes on trunk and characteristically on palms & soles.
• Condyloma lata in warm moist areas – vulva, perianal areas.
• Mucosal patches – genitalia, mouth, pharynx, larynx.
• Less common : hepatitis, renal ds, eye ds & GI abnormalities.
• Diagnosed by serological tests.
Drug therapy of syphilis
Condyloma lata -
Latent syphilis :
• Asymptomatic but presence of positive syphilis serology.
1. Early Latency : within 1 year of infection, may be
transmitted sexually.
2. Late Latency : patient no longer sexually infectious.
Tertiary syphilis :
1. Gummatous syphilis / Benign tertiary syphilis.
2. Cardiovascular syphilis.
3. Neurosyphilis.
Benign tertiary syphilis :
• Skin , mucous membrane, bone, muscle and viscera involved.
• Gumma : c/c granulomatous lesion.
• Healing occurs slowly, formation of tissue paper scars.
Gumma -
Cardiovascular syphilis :
• Aortitis which may involve aortic valve / coronary ostia.
• Clinical features – aortic incompetence, angina, aortic
aneurysm.
• Proximal aorta mainly involved.
• Surgical intervention required.
Neurosyphilis :
• Asymptomatic infection with CSF abnormalities.
• Symptomatic forms :
Meningovascular disease, Tabes dorsalis, General paresis.
Congenital syphilis
• Greater chance during early stages of disease.
• Stigmata do not develop until 4th month of pregnancy.
Manifestations:
1. Still birth
 Hepatomegaly, bone abnormalities, pancreatic fibrosis &
pneumonitis.
2. Infantile syphilis
 c/c rhinitis (snuffles) , mucocutaneous lesions.
 visceral & skeletal changes, ascites, hydrops.
3. Late / Tardive syphilis
I. Hutchinson triad - notched central incisors, interstitial keratitis
with blindness & deafness from 8th nerve injury.
II. Saber shin deformity
III. Mulberry molars
IV. Saddle nose deformity
V. Clutton joints
Drug therapy of syphilis
Congenital Syphilis
Serological tests
1. Non treponemal ( non specific ) tests :
I. Venereal Disease Research Laboratory ( VDRL ) test
II. Rapid Plasma Reagin ( RPR ) test
2. Treponemal ( specific ) tests :
I. Treponemal antigen based Enzyme Immunoassay (EIA) for IgG
& IgM.
II. T.pallidum Hemagglutination Assay ( TPHA )
III. T.pallidum Particle Agglutination Assay ( TPPA )
IV. Fluorescent Treponemal Antibody-Absorbed ( FTA-ABS ) test
 CSF examination
Management
Prophylaxis :
• Benzathine Penicillin 2.4 MU single dose before or
12 hrs within contact affords protection.
• Procaine Penicillin 2.4 MU i.m , into each buttock (
total 4.8 MU) , preceded by 1g of Probenecid helps
to prevent both Syphilis and Gonorrhea.
Treatment
Disease Treatment Alternatives
Early ( primary,
secondary and latent < 1
yr )
Benzathine Penicillin 2.4
MU i.m, 1-3 weekly inj.
Or
Procaine Penicillin 1.2 MU
i.m x 10 days
Doxycycline 100mg BD
oral x 15 days
Or
Ceftriaxone 1g i.m x 7 days
Or
Erythromycin 500mg QID
oral x 15 days
Or
Desensitization and
treatment with penicillin
Late Benzathine Penicillin 2.4
MU i.m weekly x 4 weeks
Or
Procaine Penicillin 1.2 MU
i.m x 20 days
Doxycycline
Or
Erythromycin for 30 days
Or
Ceftriaxone 1g i.m/i.v x
15 days
Or
Desensitization and
treatment with penicillin
Disease Treatment If allergy
Neurosyphilis Aqueous crystalline
Penicillin G ( 18-24 MU/d
i.v, given as 6 divided doses
or continuous infusion) for
10 -14 days
Or
Aqueous Procaine Penicillin
G ( 2-4 MU/d i.m ) +
Oral Probenecid ( 500mg
QID) , both for 10-14 days.
Desensitization and
treatment with penicillin.
• Azithromycin 2g single dose is an another alternative.
• Successful treatment → resolution of clinical signs, declining
titers of non treponemal tests ( four fold decline).
Syphilis in Pregnancy
• T.pallidum enters fetal circulation after 20th week, fetal
infection unlikely before that.
• Perinatal effects max with primary & secondary syphilis.
• Penicillin – drug of choice.
• For 1° & 2° or latent syphilis of less than 1 yr duration,
 Benzathine PenicillinG 2.4 MU i.m, as a single dose
(or)
 Crystalline Benzyl Penicillin for 10 days
• When duration is > 1 yr,
 Benzathine Penicillin 2.4 MU i.m, weekly for 3 doses is
given.
• Breast feeding is not contraindicated.
• Every neonate with congenital syphilis should be treated:
 Benzyl Penicillin for 10 days
 For Interstitial keratitis, local / systemic Glucocorticoids.
 Alternative - Erythromycin stearate
 500mg, once in 6 hrs x 2 weeks
Penicillins
• β lactum antibiotic, narrow spectrum.
• 1 MU = 0.6 g
 MOA : interfere with synthesis of cell wall by inhibiting
transpeptidases ( required for maintaining cross linking).
i.e, is bactericidal.
Benzathine PenicillinPenicillin
Pharmacokinetics :
• PnG is acid labile, destroyed by gastric acids.
• Less than 1/3 of oral dose is absorbed in active form.
• Reaches most body fluids, 60% plasma protein bound.
• T ½ = 30 min
• Rapid renal excretion –
 10% by glomerular filtration. 90% by tubular secretion.
• Tubular secretion blocked by Probenecid.
Repository Penicillin G injections
• Insoluble salts of PnG which must be given i.m, not i.v
• They release PnG slowly at site of injection
1. Procaine Penicillin G
 Plasma levels attained are low , but sustained for
12-24 hrs.
2. Benzathine Penicillin G
 Plasma conc very low , but effective for upto 4 weeks.
Adverse effects
1. Hypersensitivity
2. Local irritation
• Pain, nausea, thrombophlebitis.
• Toxicity to brain – mental confusion, muscular twitching,
convulsions, coma.
• Accidental i.v injection of Procaine Penicillin – CNS
stimulation, hallucination, convulsions, micro embolism.
3. Superinfection
4. Jarish Herxheimer reaction
Doxycycline
• Tetracycline, broad spectrum antibiotic.
 MOA :
▫ Primarily bacteriostatic.
▫ Inhibits protein synthesis by binding to 30S ribosomes .
• Intestinal absorption complete, no interference with food.
• ADR – irritative effects, phototoxicity.
• C/I in pregnancy – a/c hepatic necrosis, teeth & bone affected.
Ceftriaxone
• 3rd generation cephalosporin.
• Given parenteral.
• Bactericidal, MOA similar to penicillin.
• Longer duration of action, T ½ = 8hr
• Elimination equally in bile and urine.
• ADR – hypoprothombinemia & bleeding.
Erythromycin
MOA -
▫ Acts by inhibiting bacterial protein synthesis.
▫ It combines with 50S ribosome unit, interfere with translocation
• Is acid labile. Food delays absorption by delaying gastric emptying.
• Widely distributed in body. Crosses placenta, not BBB.
• 70-80% plasma protein bound.
• Primarily excreted in bile. Renal excretion minor.
• ADR- GI ds, hypersensitivity, reversible hearing impairment.
Treatment reactions
1. Allergy
2. Jarisch – Herxheimer Reaction :
▫ An acute febrile reaction that follows the treatment (1st
dose)
▫ Headache, malaise, myalgia, tachycardia, shivering,
exacerbations of lesions, even vascular collapse.
▫ Common in early syphilis. Rare and severe in late syphilis.
▫ May cause worsening of neurological disease, ophthalmic
disease, myocardial ischemia, laryngeal stenosis.
▫ Is due to rapid destruction of large no. of spirochetes with
release of endotoxin.
▫ Lasts for 12-72 hrs, does not need interruption of therapy.
▫ Aspirin and sedation afford relief of symptoms.
▫ Cannot be prevented by giving graduated doses of penicillin.
▫ Prevent it in cardiovascular & neurosyphilis by –
Prednisolone in single daily dose of 30mg in morning, 2 days
before starting penicillin.
3. Procaine Reaction
▫ After accidental intravenous injection of Procaine Penicillin.
▫ CNS stimulation, hallucination, fits, convulsions, fear of
impending death.
▫ Symptoms short lived.
▫ Verbal assurance & physical restraint necessary.
▫ Reaction prevented by aspiration before i.m injection to
ensure needle is not in blood vessel.
Treatment
Disease Treatment Alternatives
Early ( primary,
secondary and latent < 1
yr )
Benzathine Penicillin 2.4
MU i.m, 1-3 weekly inj.
Or
Procaine Penicillin 1.2 MU
i.m x 10 days
Doxycycline 100mg BD
oral x 15 days
Or
Ceftriaxone 1g i.m x 7 days
Or
Erythromycin 500mg QID
oral x 15 days
Or
Desensitization and
treatment with penicillin
Late Benzathine Penicillin 2.4
MU i.m weekly x 4 weeks
Or
Procaine Penicillin 1.2 MU
i.m x 20 days
Doxycycline
Or
Erythromycin for 30 days
Or
Ceftriaxone 1g i.m/i.v x
15 days
Or
Desensitization and
treatment with penicillin
Disease Treatment If allergy
Neurosyphilis Aqueous crystalline
Penicillin G ( 18-24 MU/d
i.v, given as 6 divided doses
or continuous infusion) for
10 -14 days
Or
Aqueous Procaine Penicillin
G ( 2-4 MU/d i.m ) +
Oral Probenecid ( 500mg
QID) , both for 10-14 days.
Desensitization and
treatment with penicillin.
Drug therapy of syphilis

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Drug therapy of syphilis

  • 2. Sexually Transmitted Diseases ( STD ) • Syphilis • Gonorrhea • Non Gonococcal Urethritis • Chancroid • Lymphogranuloma Venereum • Granuloma Inguinale • Vaginitis • Genital Warts • Genital Herpes • AIDS • Hepatitis B
  • 3. Syphilis • Chronic venereal infection caused by the spirochete Treponema pallidum. • Source of infection : active cutaneous or mucosal lesion in a sexual partner in early stages of syphilis.
  • 4. Classification Stage Acquired Congenital Early Primary Secondary Latent Late Latent Benign Tertiary Cardiovascular Neurosyphilis • Penicillin is the drug of choice for all stages of infection.
  • 5. Acquired syphilis : Primary syphilis : • IP – between 14 & 28 days. • A dull red macule → papular → indurated ulcer – Hard Chancre. • Inguinal lymph nodes enlarged, mobile, discrete & rubbery. • Chancre and lymph nodes : painless. • Without treatment, resolves within 2-6 weeks to leave thin atrophic scar.
  • 6. • Extra genital chancres – fingers, tongue, tonsil, nipple, anus. • Diagnosed by Dark field microscopy or direct Fluorescent Ab tests of exudates.
  • 8. Secondary syphilis : • 6-8 weeks after development of chancre when treponemes disseminate. • Mucocutaneous lesions & generalised lymphadenopathy. • Fever, malaise, headache common. • Rashes on trunk and characteristically on palms & soles. • Condyloma lata in warm moist areas – vulva, perianal areas.
  • 9. • Mucosal patches – genitalia, mouth, pharynx, larynx. • Less common : hepatitis, renal ds, eye ds & GI abnormalities. • Diagnosed by serological tests.
  • 12. Latent syphilis : • Asymptomatic but presence of positive syphilis serology. 1. Early Latency : within 1 year of infection, may be transmitted sexually. 2. Late Latency : patient no longer sexually infectious.
  • 13. Tertiary syphilis : 1. Gummatous syphilis / Benign tertiary syphilis. 2. Cardiovascular syphilis. 3. Neurosyphilis.
  • 14. Benign tertiary syphilis : • Skin , mucous membrane, bone, muscle and viscera involved. • Gumma : c/c granulomatous lesion. • Healing occurs slowly, formation of tissue paper scars.
  • 16. Cardiovascular syphilis : • Aortitis which may involve aortic valve / coronary ostia. • Clinical features – aortic incompetence, angina, aortic aneurysm. • Proximal aorta mainly involved. • Surgical intervention required.
  • 17. Neurosyphilis : • Asymptomatic infection with CSF abnormalities. • Symptomatic forms : Meningovascular disease, Tabes dorsalis, General paresis.
  • 18. Congenital syphilis • Greater chance during early stages of disease. • Stigmata do not develop until 4th month of pregnancy. Manifestations: 1. Still birth  Hepatomegaly, bone abnormalities, pancreatic fibrosis & pneumonitis.
  • 19. 2. Infantile syphilis  c/c rhinitis (snuffles) , mucocutaneous lesions.  visceral & skeletal changes, ascites, hydrops. 3. Late / Tardive syphilis I. Hutchinson triad - notched central incisors, interstitial keratitis with blindness & deafness from 8th nerve injury. II. Saber shin deformity III. Mulberry molars IV. Saddle nose deformity V. Clutton joints
  • 22. Serological tests 1. Non treponemal ( non specific ) tests : I. Venereal Disease Research Laboratory ( VDRL ) test II. Rapid Plasma Reagin ( RPR ) test 2. Treponemal ( specific ) tests : I. Treponemal antigen based Enzyme Immunoassay (EIA) for IgG & IgM. II. T.pallidum Hemagglutination Assay ( TPHA ) III. T.pallidum Particle Agglutination Assay ( TPPA ) IV. Fluorescent Treponemal Antibody-Absorbed ( FTA-ABS ) test  CSF examination
  • 23. Management Prophylaxis : • Benzathine Penicillin 2.4 MU single dose before or 12 hrs within contact affords protection. • Procaine Penicillin 2.4 MU i.m , into each buttock ( total 4.8 MU) , preceded by 1g of Probenecid helps to prevent both Syphilis and Gonorrhea.
  • 24. Treatment Disease Treatment Alternatives Early ( primary, secondary and latent < 1 yr ) Benzathine Penicillin 2.4 MU i.m, 1-3 weekly inj. Or Procaine Penicillin 1.2 MU i.m x 10 days Doxycycline 100mg BD oral x 15 days Or Ceftriaxone 1g i.m x 7 days Or Erythromycin 500mg QID oral x 15 days Or Desensitization and treatment with penicillin Late Benzathine Penicillin 2.4 MU i.m weekly x 4 weeks Or Procaine Penicillin 1.2 MU i.m x 20 days Doxycycline Or Erythromycin for 30 days Or Ceftriaxone 1g i.m/i.v x 15 days Or Desensitization and treatment with penicillin
  • 25. Disease Treatment If allergy Neurosyphilis Aqueous crystalline Penicillin G ( 18-24 MU/d i.v, given as 6 divided doses or continuous infusion) for 10 -14 days Or Aqueous Procaine Penicillin G ( 2-4 MU/d i.m ) + Oral Probenecid ( 500mg QID) , both for 10-14 days. Desensitization and treatment with penicillin.
  • 26. • Azithromycin 2g single dose is an another alternative. • Successful treatment → resolution of clinical signs, declining titers of non treponemal tests ( four fold decline).
  • 27. Syphilis in Pregnancy • T.pallidum enters fetal circulation after 20th week, fetal infection unlikely before that. • Perinatal effects max with primary & secondary syphilis. • Penicillin – drug of choice. • For 1° & 2° or latent syphilis of less than 1 yr duration,  Benzathine PenicillinG 2.4 MU i.m, as a single dose (or)  Crystalline Benzyl Penicillin for 10 days
  • 28. • When duration is > 1 yr,  Benzathine Penicillin 2.4 MU i.m, weekly for 3 doses is given. • Breast feeding is not contraindicated. • Every neonate with congenital syphilis should be treated:  Benzyl Penicillin for 10 days  For Interstitial keratitis, local / systemic Glucocorticoids.  Alternative - Erythromycin stearate  500mg, once in 6 hrs x 2 weeks
  • 29. Penicillins • β lactum antibiotic, narrow spectrum. • 1 MU = 0.6 g  MOA : interfere with synthesis of cell wall by inhibiting transpeptidases ( required for maintaining cross linking). i.e, is bactericidal.
  • 31. Pharmacokinetics : • PnG is acid labile, destroyed by gastric acids. • Less than 1/3 of oral dose is absorbed in active form. • Reaches most body fluids, 60% plasma protein bound. • T ½ = 30 min • Rapid renal excretion –  10% by glomerular filtration. 90% by tubular secretion. • Tubular secretion blocked by Probenecid.
  • 32. Repository Penicillin G injections • Insoluble salts of PnG which must be given i.m, not i.v • They release PnG slowly at site of injection 1. Procaine Penicillin G  Plasma levels attained are low , but sustained for 12-24 hrs. 2. Benzathine Penicillin G  Plasma conc very low , but effective for upto 4 weeks.
  • 33. Adverse effects 1. Hypersensitivity 2. Local irritation • Pain, nausea, thrombophlebitis. • Toxicity to brain – mental confusion, muscular twitching, convulsions, coma. • Accidental i.v injection of Procaine Penicillin – CNS stimulation, hallucination, convulsions, micro embolism. 3. Superinfection 4. Jarish Herxheimer reaction
  • 34. Doxycycline • Tetracycline, broad spectrum antibiotic.  MOA : ▫ Primarily bacteriostatic. ▫ Inhibits protein synthesis by binding to 30S ribosomes . • Intestinal absorption complete, no interference with food. • ADR – irritative effects, phototoxicity. • C/I in pregnancy – a/c hepatic necrosis, teeth & bone affected.
  • 35. Ceftriaxone • 3rd generation cephalosporin. • Given parenteral. • Bactericidal, MOA similar to penicillin. • Longer duration of action, T ½ = 8hr • Elimination equally in bile and urine. • ADR – hypoprothombinemia & bleeding.
  • 36. Erythromycin MOA - ▫ Acts by inhibiting bacterial protein synthesis. ▫ It combines with 50S ribosome unit, interfere with translocation • Is acid labile. Food delays absorption by delaying gastric emptying. • Widely distributed in body. Crosses placenta, not BBB. • 70-80% plasma protein bound. • Primarily excreted in bile. Renal excretion minor. • ADR- GI ds, hypersensitivity, reversible hearing impairment.
  • 37. Treatment reactions 1. Allergy 2. Jarisch – Herxheimer Reaction : ▫ An acute febrile reaction that follows the treatment (1st dose) ▫ Headache, malaise, myalgia, tachycardia, shivering, exacerbations of lesions, even vascular collapse. ▫ Common in early syphilis. Rare and severe in late syphilis. ▫ May cause worsening of neurological disease, ophthalmic disease, myocardial ischemia, laryngeal stenosis.
  • 38. ▫ Is due to rapid destruction of large no. of spirochetes with release of endotoxin. ▫ Lasts for 12-72 hrs, does not need interruption of therapy. ▫ Aspirin and sedation afford relief of symptoms. ▫ Cannot be prevented by giving graduated doses of penicillin. ▫ Prevent it in cardiovascular & neurosyphilis by – Prednisolone in single daily dose of 30mg in morning, 2 days before starting penicillin.
  • 39. 3. Procaine Reaction ▫ After accidental intravenous injection of Procaine Penicillin. ▫ CNS stimulation, hallucination, fits, convulsions, fear of impending death. ▫ Symptoms short lived. ▫ Verbal assurance & physical restraint necessary. ▫ Reaction prevented by aspiration before i.m injection to ensure needle is not in blood vessel.
  • 40. Treatment Disease Treatment Alternatives Early ( primary, secondary and latent < 1 yr ) Benzathine Penicillin 2.4 MU i.m, 1-3 weekly inj. Or Procaine Penicillin 1.2 MU i.m x 10 days Doxycycline 100mg BD oral x 15 days Or Ceftriaxone 1g i.m x 7 days Or Erythromycin 500mg QID oral x 15 days Or Desensitization and treatment with penicillin Late Benzathine Penicillin 2.4 MU i.m weekly x 4 weeks Or Procaine Penicillin 1.2 MU i.m x 20 days Doxycycline Or Erythromycin for 30 days Or Ceftriaxone 1g i.m/i.v x 15 days Or Desensitization and treatment with penicillin
  • 41. Disease Treatment If allergy Neurosyphilis Aqueous crystalline Penicillin G ( 18-24 MU/d i.v, given as 6 divided doses or continuous infusion) for 10 -14 days Or Aqueous Procaine Penicillin G ( 2-4 MU/d i.m ) + Oral Probenecid ( 500mg QID) , both for 10-14 days. Desensitization and treatment with penicillin.