DRUGS USED FOR THE TREATMENT OF SYPHILIS & GONORRHEA

PROF.AZZAEl-Medany

OBJECTIVES OBJECTIVES At the end of lecture, the students should able to : At the end of lecture, the students should able to : List The drugs used in the List The drugs used in the treatment of syphilis treatment of syphilis List the drugs used in treatment of gonorrhea. Describe The mechanism of action, adverse effects of & clinical indication of each drug Describe The mechanism of action, adverse effects of & clinical indication of each drug

OBJECTIVES ( continue) Describe the contraindications of each drug used Describe the contraindications of each drug used Describe the recommended regimens used for treatment of syphilis & gonorrhoea Describe the recommended regimens used for treatment of syphilis & gonorrhoea Describe the alternative treatments in allergic patients to certain antibiotics Describe the alternative treatments in allergic patients to certain antibiotics

6 Syphilis Definition Sexually acquired infection Sexually acquired infection Etiologic agent: Treponema pallidum Etiologic agent: Treponema pallidum Disease progresses in stages Disease progresses in stages May become chronic without treatment May become chronic without treatment Epidemiology

7 Treponema pallidum Pathogenesis Source: CDC/NCHSTP/Division of STD Prevention, STD Clinical Slides Electron photomicrograph, 36,000 x.

Classification Of Syphilis A primary stage ( a single sore ( a chancre ) ) A primary stage ( a single sore ( a chancre ) )

Secondary Stage Skin rash & mucous membranes lesions Skin rash & mucous membranes lesions

10 Secondary Syphilis: Palmar/Plantar Rash Clinical Manifestations 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

11 Tertiary (Late) Syphilis Approximately 30% of untreated patients progress to the tertiary stage within 1 to 20 years Approximately 30% of untreated patients progress to the tertiary stage within 1 to 20 years Rare because of the widespread use of antibiotics Rare because of the widespread use of antibiotics Manifestations Manifestations Cardiovascular syphilis Cardiovascular syphilis Clinical Manifestations

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.

14 Congenital Syphilis - Perforation of Palate Clinical Manifestations Source: CDC/ NCHSTP/ Division of STD Prevention, STD Clinical Slides

15 Neurosyphilis - Spirochetes in Neural Tissue Source: CDC/ NCHSTP/ Division of STD Prevention, STD Clinical Slides Silver stain, 950x

Therapy of syphilis

Penicillins ( β-lactam antibiotic

PENICILLINS PENICILLINS Bactericidal Drugs Bactericidal Drugs Mechanism of action Mechanism of action Inhibit the synthesis of bacterial cell wall. Inhibit the synthesis of bacterial cell wall.

Preparations of penicillins used for treatment of syphilis Penicillin G (IV ) Penicillin G (IV ) Procaine penicillin (IM ) Procaine penicillin (IM ) Benzathine penicillin (IM ) Benzathine penicillin (IM )

Penicillin G Penicillin G Short duration of action Short duration of action ( 4-6 hrs) ( 4-6 hrs) Acid unstable Acid unstable Penicillinase sensitive Penicillinase sensitive

Procaine penicillin Procaine penicillin Long acting (24-48hrs) Long acting (24-48hrs) Acid unstable Acid unstable Penicillinase sensitive Penicillinase sensitive

Benzathine penicillin Long acting Long acting ( every 3-4 weeks) ( every 3-4 weeks) Acid unstable Acid unstable Penicillinase sensitive Penicillinase sensitive

Adverse effects of penicillins Adverse effects of penicillins Hypersensitivity Hypersensitivity Nephritis Nephritis Convulsions with high doses or in renal failure Convulsions with high doses or in renal failure

24 Therapy for Primary, Secondary, and Early Latent Syphilis Benzathine penicillin 2.4 million units IM in a single dose Benzathine penicillin 2.4 million units IM in a single dose I

For Allergic Patients To Penicillins Tetracyclines such as: Tetracyclines such as:DoxycyclineTetracycline Macrolides such as: Macrolides such as:Azithromycin Cephalosprins such as : Cephalosprins such as :Ceftriaxone cefixime cefixime

TETRACYCLINES Doxycycline Doxycycline Well absorbed orally Well absorbed orally Long-acting Long-acting

Tetracycline Absorption after oral administration ( 60-70%) Absorption after oral administration ( 60-70%) Given every 6hrs. Given every 6hrs.

Mechanism of action Bacteriostatic Bacteriostatic Inhibit bacterial protein synthesis by reversibly binding to 30 S bacterial ribosomal subunits. Inhibit bacterial protein synthesis by reversibly binding to 30 S bacterial ribosomal subunits.

Tetracyclines in treatment of syphilis Doxycycline Doxycycline 100 mg orally twice daily for 14 days 100 mg orally twice daily for 14 days Tetracycline 500 mg orally 4 times daily for 14 days

Contraindication: 1.Children ( below 10 years) 2.Pregnancy Nursing mothers Side effects: 1-gastric upset( nausea, vomiting, diarrhea) 2-Effects on calcified tissues (discoloration of teeth)&bone deformity 3-Hepatotoxicity 4-Phototoxicity 5-vestibular problems (vertigo,nausea, vomiting) 6-Superinfections Side Effects and contraindication

MACROLIDES (Azithromycin) Mechanism of action Mechanism of action Inhibits bacterial protein synthesis by binding to bacterial 50S ribosomal subunits Inhibits bacterial protein synthesis by binding to bacterial 50S ribosomal subunits

Pharmacokinetics Acid stable Acid stable Penetrates into most tissues except CSF Penetrates into most tissues except CSF T1/2 2-4 days T1/2 2-4 days Once daily dose Once daily dose Should given 1hour before or 2 hours after meals Should given 1hour before or 2 hours after meals Does not inactivate cytochrome P450 Does not inactivate cytochrome P450

ADVERSE EFFECTS. Gastric upset Gastric upset

Indication in syphilis 2g single dose is effective in treatment of early syphilis 2g single dose is effective in treatment of early syphilis

Cephalosporinsns β-lactam antibiotics 3 rd Generation cephalosporins e.g. cefixime e.g. Ceftriaxone Mechanism of action Inhibits bacterial cell wall synthesis Bactericidal

Adverse effects Allergic manifestations Allergic manifestations Thrombophilibitis Thrombophilibitis Superinfection Superinfection Diarrhea Diarrhea

Therapy for Neurosyphilis Aqueous crystalline penicillin G million units per day, administered as 3-4 million units IV every 4 hours or continuous infusion for days IV Aqueous crystalline penicillin G million units per day, administered as 3-4 million units IV every 4 hours or continuous infusion for days IV Alternative regimen (if compliance can be ensured): 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 days Procaine penicillin 2.4 million units IM once daily PLUS Probenecid 500 mg orally 4 times a day, both for days

Therapy for Neurosyphilis Aqueous crystalline penicillin G million units per day, administered as 3-4 million units IV every 4 hours or continuous infusion for days IV Aqueous crystalline penicillin G million units per day, administered as 3-4 million units IV every 4 hours or continuous infusion for days IV Alternative regimen (if compliance can be ensured): 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 days Procaine penicillin 2.4 million units IM once daily PLUS Probenecid 500 mg orally 4 times a day, both for days

Therapy for Syphilis in Pregnancy Treat with penicillin according to stage of infection. Treat with penicillin according to stage of infection. Erythromycin is no longer an acceptable alternative drug in penicillin-allergic patients. Erythromycin is no longer an acceptable alternative drug in penicillin-allergic patients. Patients who are skin-test- reactive to penicillin should be desensitized in the hospital and treated with penicillin. Patients who are skin-test- reactive 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 NO SYMPTOM S NO 60% of Females DON’T KNOW they have it. 20% - 40% of Males DON’T KNOW they have it. BUT: Does spread to partners Does damage the body

:Recommended regimens ( 1 st line treatment) :Recommended regimens ( 1 st line treatment) Uncomplicated gonorrheal infections Uncomplicated gonorrheal infections Single –dose treatment with 3 rd generation cephalosporins 500 mg of ceftriaxone, IM 500 mg of ceftriaxone, IM 500mg of Cefotaxime IMI 500mg of Cefotaxime IMI

Macrolides Azithromycin as a single oral dose 1 g.in combination with ceftriaxone 250 mg IMI Azithromycin as a single oral dose 1 g.in combination with ceftriaxone 250 mg IMI Or high dose 2g. As a single oral dose Or high dose 2g. As a single oral dose In pregnant & breast feeding mothers azithromycin is given as a single oral dose 1g In pregnant & breast feeding mothers azithromycin is given as a single oral dose 1g

FLUOROQUINOLONES FLUOROQUINOLONES Single oral dose of : Ciprofloxacin 500 mg orally Ciprofloxacin 500 mg orally Ofloxacin 400 mg orally Ofloxacin 400 mg orally Levofloxacin Levofloxacin

MECHANISM OF ACTION of fluoroquinolones All are bactericidal All are bactericidal Inhibit DNA synthesis by inhibiting DNA gyrase enzyme Inhibit DNA synthesis by inhibiting DNA gyrase enzyme

ADVERSE EFFECTS Diarrhea nausea headache dizziness GIT upset phototoxicity arthropathy

CONTRAINDICATIONS Pregnancy Pregnancy Nursing mothers Nursing mothers Adolescent under 18 years Adolescent under 18 years

Alternative treatment in allergic patients to 1 st line treatment Spectinomycin Spectinomycin 2g IMI ( once ) 2g IMI ( once )

Mechanism of action Inhibits protein synthesis by binding to 30 S ribosomal subunits Inhibits protein synthesis by binding to 30 S ribosomal subunits

1.Pain at the site of injection Adverse Effects Nephrotoxicity (not common) 2. Fever Nausea

CONTINUE Complicated gonorrheal infections Complicated gonorrheal infections Spread through blood stream  EYE Joints Joints Heart valves Heart valves Brain Brain

Antibiotics that are no longer recommended for gonorrhea treatment

Continue Sulfonamides Sulfonamides Penicillins Penicillins Tetracyclines Tetracyclines Oral cephalosporins 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 Silver nitrate Its germicidal effects are due to precipitation of bacterial proteins by liberated silver ions 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 ) 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. 0.5% ointment for treatment & prevention of corneal & conjunctival infections. Put into conjunctival sac immediately after birth ( no later 1 hr after delivery ) Put into conjunctival sac immediately after birth ( no later 1 hr after delivery )