PHARMACOLOGY in Std(Drugs and their action in sexually transmitted disease).ppt

Drugs and their action in sexually transmitted infection

1. PHARMACOLOGY
IN SEXUALLY TRANSMITTED
INFECTIONS
DR. S. SARANYA RAJEE
PG MD DVL

2. FLOW OF TALK:
•ANTIBACTERIAL
•ANTI VIRAL
•ANTI FUNGAL
•ANTI PARASITICAL
•ANTI PROTOZOAL
•THERAPY FOR WART
•IMMUNOLOGICAL THERAPY

3. ANTI BACTERIAL AGENTS

4. PENICILLIN
•BETA LACTAM GROUP
•PENICILLIN G –from Penicillium chrysogenum
•First= dicloxacillin, oxacillin -GP cocci (ex.
MSSA)
•Second = aminopenicillins (ampicillin and
amoxicillin) -GN bacilli and GP cocci
•Third and Fourth = carboxypenicillins
(carbenicillin) and ureidopenicillins
(piperacillin)-
antipseudomonal activity (piperacillin
>carbenicillin)
Beta lactam ring
binds to
bacterial
enzyme DD-
transpeptidase
(-) formation of
peptidoglycan
cross-links in
bacterial
cell wall
(-) Cell wall
synthesis
Mechanism of Action:

5. MECHANISM OF RESISTANCE:
•Hydrolysis by Beta-lactamases
•Modification of penicillin bindingsites
•Reduction in outer membrane permeability
preventing drug from reaching target site (ex. GN
bacteria)
PREG CAT-B
ADVERSE EFFECTS:
•Hypersensitivity
•Urticaria/angioedema
•SJS/TEN rarely (predominantly IV
forms)
•Potential cross-reaction with
cephalosporins and other beta-
lactam antibiotics
•J-H reactions

6. INDICATIONS:
•Syphilis
BENZATHINE BENZYL
PENICILLIN -2.4 million IU
deep im
( half In 2 separate sites )
PROCAINE PENICILLIN-1.2
million IU im daily
AQUEOUS BENZYL
PENICILLIN
Primary / Secondary /
Early latent
single dose OD x10 days
Late latent/ benign
tertiary/unknown
duration
Once weekly for 3
consecutive weeks
OD x 20 days
Neurosyphilis
Pregnancy
OD + Probenecid 500 mg
QID x 10-14 days
12-24 million IU iv daily In
doses of 2-4 million IU Q4H
x 14 days
Early congenital 50000 IU/kg im single
dose x 10 days
100000-150000 IU/kg/ day
as 50000 IU/kg/ day iv every
Q12H upto day 7 of life then
Q8H x 10 total days
Late congenital 200000-300000 IU/kg/ day
iv/im as 50000 IU/kg/ day iv
every Q4-6H x 10-14 days

7. •Gonococcal infections:
-Amoxicillin 500mg TDS x 7 days
( also safe In pregnancy )

8. CEPHALOSPORIN
•byproducts of the mold
Cephalosporium acremonium
•Third generation = cefixime,
cefotaxime, ceftazidime,
ceftriaxone –increased GN
activity (because of greater
beta-lactamase stability), but
less GP activity
Same as
penicillins,
but have a
6-
membered
dihydrothia
zine
ring
(-) cell wall
synthesis
PREG CAT-B
Mechanism of Action:

9. INDICATIONS:
•Syphilis-ceftriaxone 1g iv x 10 days
•Chancroid-ceftriaxone 250 mg im single dose
•PID-ceftriaxone 250 mg im OD + DOXY + METRO
•Gonococcal infection -cefixime400 mg single dose
-ceftriaxone 125 mg im single dose

10. FLUOROQUINOLONES
inhibitionof
DNA gyrase
(bacterial
topopisomera
se II) +/-
topoisomeras
e IV
Interfere
with
bacterial
DNA
replication
BACTERICI
DAL
ACTIVITY
GP (target -topoisomerase IV)
GN (target -DNA gyrase)
ciprofloxac
in,
ofloxacin
First-and
second-
generation
quinolones
target DNA
gyrase
GN
organisms
Ciprofloxacin, ofloxacin and levofloxacin have some
activity against atypical mycobacteria
Mechanism of Action:

11. MECHANISM OF RESISTANCE:
•Alteration of drug target
mechanism
•Decreasing intra bacterial
accumulation via drug efflux pump
INDICATIONS:
•Chancroid-Ciprofloxacin 500 mg BD x 3 days
•Gonococcal infection-ofloxacin 300 mg BD x 7
days
-ciprofloxacin500 mg
single dose
PREG CAT-C
ADVERSE EFFECTS:
•Tendinitis/rupture
•Prolonged QTc interval
•Peripheral neuropathy
•CNS effects—seizures, pseudotumor cerebri,
nervousness, tremors, depression, suicidal
thoughts
•Hepatotoxicity

12. MACROLIDES Bind to 50s
subunit of
bacterial
ribosome,
inhibiting
RNA
dependent
protein
synthesis
ANTI INFLAMMATORY
Erythromycin
Clarithromycin
Azithromycin
1.Modification of drug target via methylation of
rRNA
nucleotides or mutation of ribosomal components
2. Decreasing intra bacterial accumulation
via drug efflux pump
Mechanism of Resistance
Mechanism of Action:
PREG CAT-B

13. INDICATIONS:
•Chancroid
-Azithromycin 1 g single dose
-Erythromycin 500 mg QID x 7 days
•Granuloma inguinale
-Azithromycin 1 g PO on day 1 followed by
500 mg PO OD
-Erythromycin 500 mg QID
•LGV
-Erythromycin 500 mg QID x 14 days
•Syphilis(allergic to penicillin + pregnant)
-Erythromycin 500 mg QID
Congenital ( >1 month of life )-75-12.5 mg
/kg QID x 14 days
•Urethritis
-Azithromycin 1 g single dose
-Erythromycin 500mg QID x 7 days (also used
In pregnancy )

14. ADVERSE EFFECTS:
•QTc prolongation
•Elevated LFT/hepatitis
•Clostridium difficile-associated
disease
•Urticaria, angioedema, SJS/TEN,
DRESS, vasculitis
•aggravate weakness in patients
with myasthenia gravis

15. TETRACYCLINES
•GP and GN skin infections, including MRSA
•Chlamydia spp.,
•Rickettsia spp.,
•Mycoplasma spp.,
•atypical mycobacteria,
•spirochetes and Lyme disease
Bind to 30s
subunit of
bacterial
ribosome
inhibiting
RNA
dependent
protein
synthesis
ANTI
INFLAMMATORY
Mechanism of Action:
Tetracycline
Doxycycline
Minocycline
PREG CAT-D

16. MECHANISM OF RESISTANCE:
•Decreasing intra bacterial accumulation via decreasing influx or increasing efflux
•Alteration of drug target
INDICATIONS:
•Non gonococcal urethritis
-Doxycycline 100 mg BD x 7 days
-Tetracycline 500 mg QID x 7 days
•Granuloma inguinale-
-Doxycycline 100 mg BD
-Tetracycline 500 mg QID
•PID
-Doxycycline 100 mg BD x 14 days
-Tetracycline 500 mg QID x 14 days
ALLERGIC TO
PENICILLIN/ NON
PREGNANT
EARLY LATE (late latent / benign
tertiary/ neuro)
Doxycycline 100 mg BD x 14 days BD x 30 day
Tetracycline 500 mg QID x 14 days QID x 30 days
LGV
-Doxycycline 100 mg BD x 14 days
-Tetracycline 500 mg QID x 14 days
Syphilis

17. ADVERSE EFFECTS:
•Nephrogenic diabetes insipidus
(demeclocycline only)
•Tissue hyperpigmentation
(minocycline)
•Pseudotumor cerebri (alone or
with
isotretinoin)
SJS/TEN, anaphylaxis rare
Minocycline only—DRESS,
serumsickness like reaction,
drug-induced, LE, vasculitis

18. COTRIMOXAZOLE
trimethopri
m
•Dihydrofol
ate
reductase
inhibitor
sulfametho
xazole
•dihydropt
eroate
synthetase
inhibitor
TMP-
SMX
•decreased
tetra
hydrofolic
acid
•decreased
bacterial
nucleic
acid and
protein
synthesis
GP cocci (MRSA, Enterococcus faecalis and
S. pyogenes)
H. influenzae,
Pneumocystis jirovecii
Nocardia spp.
Chlamydia
various GN

19. •Alteration of drug target via acquired mutations and/or plasmid acquisition
•Decreasing intra bacterial accumulation via active drug efflux
•Auxotrophic bacteria (naturally resistant)
Mechanism of Resistance
PREG CAT-D
•ADVERSE EFFECTS:
•agranulocytosis, Aplastic anemia, ITP
•severe hepatitis
•Hyponatremia, hyperkalemia
•SJS/TEN
•INDICATIONS:
•Granulomainguinale-Cotrimoxazole ( 80/400) 2
BD x 14 days
•Recurrent and persistent urethritis

20. SPECTINOMYCIN
•Aminocyclitolclass of drug
•Derived from streptomyces spectabilis
•Used In Gonorrhea (uncomplicated) ( all mucosa ) infection-2g im
single dose
•DGI-2g im BD x 7 days
•Meningitis , endocarditis-25 mg/kg im single dose to max 75 mg
SIDE EFFECTS:
•Urticaria, Chills, fever, nausea, insomnia
Bind to 30s
subunit of
bacterial
ribosome
inhibiting
protein
synthesis
Mechanism of Action:

21. KANAMYCIN:
•Aminoglycosideantibiotic
•Derived from streptomyces kanamyceticus
•Against GN organisms
•Gonococcal infections-2g im single dose
•Meningitis , endocarditis-25 mg/kg im single dose to max 75 mg
SIDE EFFECTS:
•Tinnitus
•Ototoxicity
•Nephrotoxicity
•Allergic reaction
•Neuromuscular blockade
Bind to 30s
subunit of
bacterial
ribosome
inhibiting
protein
synthesis
Mechanism of Action:
PREG CAT-D

22. ANTI VIRAL DRUGS

24. ACYCLOVIR, VALACYCLOVIR, FAMCICLOVIR
•FDA-APPROVED INDICATIONS
•Herpes Simplex Infections
Primary episode-Acyclovir 200 mg 5 times daily x 7 days/ 400 mg TDS x 7 days
-valacyclovir 1 g BD x 7 days
-Famciclovir 250 mg TDS x 7 days
Recurrent episodes-Acyclovir 200 mg 5 times daily x 5 days/ 400 mg TDS x 5 days / 800 mg BD x
5 days
-valacyclovir 500 mg BD x 5 days / 1g OD x 5 days
-Famciclovir 125 mg BD x 5 days
Suppressive therapy-Acyclovir 400 mg BD
-Valacyclovir 500 mg OD / 1 g OD
-Famciclovir 250 mg BD
PLHA-Acyclovir 400 mg 3-5 times daily until clinical resolution
Severe disease-Acyclovir 5-10 mg/kg iv Q8H for 5-7 days / until clinical resolution
PREG CAT-B

25. •Chicken pox
•Herpes zoster
•Other Dermatologic Uses
•Recurrent erythema multiforme (presumed/proven caused by
HSV)
•Other subsets of herpes simplex infections

26. ADVERSE EFFECTS:
•Crystal induced nephropathy -iv rapid administration ( high
intratubular precipitation of crystals-acute renal injury -24-48
hrs)
•Thrombotic microangiopathy in immunocompromised patients
•Neurotoxicity with higher doses

27. FOSCARET, CIDOFOVIR:
•used in acyclovir resistant herpes infection
•Interfere with exchange of pyrophosphate by binding to a site
on viral DNA polymerase
•Doesn’t need viral thymidine kinase for activation
•topical -1% or 3% cidofovir ointment
•iv-foscarnet 40 mg /kg TDS / 60 mg / kg BD

28. ANTI FUNGAL DRUGS

29. FLUCONAZOLE
•Triazole
INDICATIONS:
•Vulvovagial candidiasis
-Fluconazole 150 mg PO single dose
•Candidal Balanoposthitis
-Fluconazole 150 mg PO single dose
(-)14-
alpha
demethylas
e
(-)
ergosterol
synthesis
Fungal cell
membrane
synthesis
and fungal
cell
replication
ADVERE EFFECTS:
•Hepatotoxicity
•QT prolongation
PREG CAT-unrated, (moderate –high risk )
Mechanism of Action:

30. INTRAVAGINAL
•MICONAZOLE / CLOTRIMAZOLE 200 mg daily x 3 days
•CLOTRIMAZOLE 500 mg single dose
•NYSTATIN 100000 IU daily x 14 days

31. TOPICAL AZOLES:
•2 % clotrimazole
•Cream, gel, spray, lotion, solution, pessary
•Dermatophyte infections
•Candidal infections
•Adverse effects: local irritation, itching, burning

32. SERTACONAZOLE -2 %
•Benzothiophene imidazole anti fungal
•More effective than clotrimazole -early response & significant
reduction in pruritus
•Anti inflammatory property-reduce cytokines secretion from
activated lymphocytes, histamine release from mast cells,
release of PG E2.
•additional fungicidal property-binds to non sterol lipids on the
fungal membrane-interferes with ligand -cell death

33. ANTI PROTOZOAL DRUGS

34. NITROIMIDAZOLE
•Secnidazole / Tinidazole /
Metronidazole
•Free radical anions (-) DNA
synthesis
•PFOR -Pyruvate ferredoxin
oxidoreductase converts
pyruvate to Acetyl CoA ,which
then cause transfer of pair of
electrons to ferredoxin —
reduce metronidazole ( activated
form )

35. SIDE EFFECTS
•Diarrhea
•Vomiting
•Abdominal cramp
•Vulvovaginal candidiasis
•dysgeusia
INDICATIONS:
•Bacterial vaginosis
–metronidazole 2g PO single dose
-PREGNANCY-metro 200 or 250 mg PO TD x 7 days ( after first
trimester ) 2 g PO single dose ( first trimester )
•Trichomoniasis
–metronidazole 2g PO single dose / 400 mg or 500 mg PO BD x 7
days
-tinidazole 2 g PO single dose / 500 mg BD x 5 days
•Amoebiasis
•PID–Metronidazole 400-500 mg BD x 14 days

36. ANTI-PARASITE

37. IVERMECTIN
•derived from
Streptomyces avermitilis
INDICATIONS:
•FDA APPROVED
•intestinal strongyloidiasis
•Onchocerciasis
•OFF LABEL
•Scabies-200 mcg/kg
•Pediculosis
•Demodicosis
•cutaneous larva migrans
Glutam
ate/
GABA-
gated
chloride
ion
channel
s (-)
increas
ed
permea
bility
hyperp
olarizati
on of
the
nerve
or
muscle
cells
Death
of the
parasite
ADVERSE EFFECTS:
-mazzoti reaction (ochocerchiasis)
-Pruritus
-Fever
-Lymphadenopathy or lymph node
tenderness
Mechanism of Action:

38. TOPICALS:
•1 % GBHC:
GABA-gated chloride ion
channels (-)
-single application ( neck to toe
) overnight
ADVERSE EFFECTS:
Neurotoxicity, irritability,
insomnia, ataxia, tremor
•PRECIPITATED SULPHUR
6%
•5 % PERMETHRIN
•10 % CROTAMITON
•25 % BENZYL BENZOATE
•0.5 % MALATHION

39. WART THERAPY:

40. MECHANISM OF ACTION:
(-) MITOTIC
SPINDLE
FORMATION
(-) CELL DIVISION
NECROSIS / CELL DEATH
PODOPHYLLIN

41. •10-25% in tincture benzoin
•root of podophyllum emodii or peltatum
•active ingredient –podophyllotoxin , alpha & beta phelltatum
•side effects of the drug-lignanssuch as quercetin
•once or twice weekly
•< 0.5 ml or 10 sq.cm / sitting
•washed off after 4–6 hours x 6 weeks
•SIDE EFFECTS: local irritation, neurotoxicity

42. PODOFILOX -0.5 %
•suitable for home treatment
•3 days ON , 4 days OFF therapy/ week x 4 cycles
•Less side effects
•MONOCHLOROACETIC AND TRICHLOROACETIC ACID
•5 FLUROURACIL
•GREEN TEA CATECHINS

43. IMMUNOTHERAPY:
•TOPICAL-imiquimod, BCG
•INTRALESIONAL-BCG, PPD, CANDIDAL Ag, Trichophyton,
measles, MMR, MIP
•ORAL-zinc, levamisole, cimetidine
Toll like receptor (TLR-7
and TLR-8).
nuclear factor kappa B
(NF-kB)
IFN-gamma,TNF-alpha,
IL-2,6,8, and
12, G-CSF, GM-CSF

44. IMIQUIMOD
•5% cream
•3 times / week on alternate days x 16 weeks
•washed off 6-10 hrs after application
•side effects -local irritation

45. PROBIOTICS:
•Live micro organisms which when administered in adequate
amounts, confer a health benefit on the host
•Lactobacillus reuteri, casei, rhamnosus, acidophilus
•Streptococcus spp,
•Bifidobacterium infantis, lactis, longum
•Sacharomyces boulardii

47. USES:
•improve digestion
•Reduce diarrhoea associated with antibiotic therapy
•Improves Lactose tolerance
•Enhance immune function
•Reduce development of allergy in children
•Reduce H.pylori colonisation of the stomach
•Reduce relapse of IBD
•Used in bacterial vaginosis

48. THANK YOU