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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 )