Drug therapy of syphilis

Syphilis

a Pharmacology topic for MBBS

1. Drug Therapy Of Syphilis Labeeb 102

2. Sexually T ransmitted Diseases ( STD ) Syphilis Gonorrhea Non Gonococcal Urethritis Chancroid Lymphogranuloma V enereum 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.

7. Oral chancre Hard Chancre

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.

10. Condyloma lata -

11. L atent syphilis : Asymptomatic but presence of positive syphilis serology. Early Latency : within 1 year of infection, may be transmitted sexually. Late Latency : patient no longer sexually infectious .

12. Tertiary syphilis : Gummatous syphilis / B enign tertiary syphilis. Cardiovascular syphilis. Neurosyphilis .

13. Benign tertiary syphilis : Skin , mucous membrane, bone, muscle and viscera involved. Gumma : c/c granulomatous lesion . Healing occurs slowly, formation of tissue paper scars .

14. Gumma -

15. Cardiovascular syphilis : Aortitis which may involve aortic valve / coronary ostia . Clinical features – aortic incompetence, angina, aortic aneurysm. Proximal aorta mainly involved. Surgical intervention required .

16. Neurosyphilis : Asymptomatic infection with CSF abnormalities. Symptomatic forms : Meningovascular disease, Tabes dorsalis , General paresis .

17. Congenital syphilis Greater chance during early stages of disease. Stigmata do not develop until 4 th month of pregnancy . Manifestations : Still birth Hepatomegaly, bone abnormalities, pancreatic fibrosis & pneumonitis.

18. Infantile syphilis c/c rhinitis (snuffles) , mucocutaneous lesions. visceral & skeletal changes, ascites, hydrops . Late / Tardive syphilis Hutchinson triad - notched central incisors, interstitial keratitis with blindness & deafness from 8 th nerve injury. Saber shin deformity Mulberry molars Saddle nose deformity Clutton joints

19. Congenital Syphilis

20. Serological tests Non treponemal ( non specific ) tests : Venereal Disease Research Laboratory ( VDRL ) test Rapid Plasma Reagin ( RPR ) test Treponemal ( specific ) tests : Treponemal antigen based E nzyme Immunoassay (EIA) for IgG & IgM . T. pallidum Hemagglutination Assay ( TPHA ) T. pallidum Particle Agglutination Assay ( TPPA ) Fluorescent Treponemal Antibody-Absorbed ( FTA-ABS ) test CSF examination

21. 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.

22. 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

23. 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.

24. Azithromycin 2g single dose is an another alternative. Successful treatment → resolution of clinical signs, declining titers of non treponemal tests ( four fold decline ).

25. Syphilis in Pregnancy T. pallidum enters fetal circulation after 20 th 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

26. 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

27. Penicillins β l actum 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.

28. Benzathine Penicillin Penicillin

29. 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 .

30. 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 Procaine Penicillin G Plasma levels attained are low , but sustained for 12-24 hrs. Benzathine Penicillin G Plasma conc very low , but effective for upto 4 weeks.

31. Adverse effects Hypersensitivity 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. Superinfection Jarish Herxheimer reaction

32. 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.

33. Ceftriaxone 3 rd generation cephalosporin . G iven parenteral. Bactericidal, MOA similar to penicillin. Longer duration of action, T ½ = 8hr Elimination equally in bile and urine. ADR – hypoprothombinemia & bleeding.

34. 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.

35. Treatment reactions Allergy Jarisch – Herxheimer Reaction : An acute febrile reaction that follows the treatment (1 st 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.

36. 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 d ays before starting penicillin.

37. 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.

38. 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

39. 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.

40. Thank You