GYN/Final: Anti-protozoal drugs Flashcards
list some protozoal infections in humans
amebiasis malaria trypanosomiasis toxoplasmosis giardiasis
list the mixed amebicides
*effective against?
Metronidazole
Tinidazole
Eff against: luminal and systemic forms of dz
List the luminal amebicides
*site of action
Iodoquinol
Paromycin
site of action=lumen of bowel
list the systemic amebicides
*site of action
Chloroquine
Dehydroemetine
*site of action=intestinal wall and livre
- why are protozoal infections less easily treatable vs bacterial infections
- why does tx lead to serious toxic SE
- protozas are unicellular with similar metabolic processes closer to human cells vs prokaryotic bacteria
- why tx causes serious toxic effects in host
are most anti-protozoal agents safe in pregnancy
no
Metronidazole
- chem structure
- indications (main ones)
- other clinical indiactions (9)
- available forms (4)
- MOA
- kinetics: two hallmarks of the drug, metabolized
- SE: MC and then others
- pregnancy and BF
Drug has a nitro group***
inds: mainstay tx for anaerobic infections + protozoal infections
* *Anaerobic: trichomonas vaginalis, gardnerella vaginalis, bacterioids gragilis, Clostridium, C. diff (not first line) and H. pylori
**Anti-protozoal: Amebiasis and Giardiasis
OTHER USES:
- bone and joint infections
- intraabdomainl infections
- CNS infs–including brain abscess
- Endocarditis
- GYN infections
- Resp infections
- skin infections
- colorectal surgical prophylaxis
- Dental
FORMS:
- PO
- IV
- topical gel for dermatologic
- vaginal gel
MOA:
- nitro group acts as an electron acceptor–>forming free radicals that are toxic to microbes–>causes DNA to lose helical structure–>inhibits protein synthesis–>cell death
- kills the trophozoites in amebia infections
KINETICS:
- well absorbed and almost 100% bioavailable PO
- Excellent tissue penetration
*metabolized by liver: CYP450—- if taken with CYP450 inducers it will cause metronidazole tx failure EX phenobarbital
SE:
- MC=N/D, abd cramps and metallic taste
- others:
- dark urine
- stomatitis (painful swelling and sore throat)
- neuro: parasthesias, seizure, dizziness (with high doses but its rare)
- Disulfiram reaction with ETOH (instruct PT to not drink)
- QTc»_space;> and torsades
- Renal inhibition of Lithium
Pregnancy: controversial— Cat B. and recc ONLY IF NEEDED
**should discontinue BF during and 3 days following tx
what happens if metronidazole is taken with a CYP450 inducer drug? inhibitor drug?
inducer=cause tx failure of metronidazole bc enhances rate of metabolism
inhibitor=prolong T 1/2 of metronidazole
Disulfiram-like rxn
-describe
Disulfiram also called antabuse
- drug used to tx ETOH disorder
- works by interfering with the metabolism of ETOH
- –allowing acetaldehyde to accumulate
- –high levels of acetaldehyde=uncomfortable s/s like flushing, n/v, diaphoresis and palpitations
**metronidazole**
does NOT interfere with metablism of ETOH and does NOT increase levels of acetaldehyde
BUT
it does cause a disulfiram-like rxn
what drugs taken with metronidazole cause a disulfiram-like rxn (3)
- ETOH
- Trimethoprim-sulfa (bactrim) IV
- tipranavir cough syrups/cold medicine
Tinidazole
-MOA
-uses
just like metronidazole but its more $$$$
uses:
- amebiasis
- amebic liver abscess
- giardiasis
- trichomonas
after tx of invasive or extraintestinal amebic dz, how do you now treat the asymptomatic colonization state?
with LUMINAL drugs– Iodoquinol and Paromycin
Iodoquinol
- effective against?
- se
effective against: E. Histolytica in luminal trophozoite and cyst forms
USED: during asympto colonization phase
SE:
- rash
- diarrhea
- dose-related peripheral neruopathy—such as optic neuritis
- avoid long term use**
Paromycin
- structure
- drug class
- spectrum
- uses
- se
Aminoglycoside antibitoic
uses: luminal forms of E. histolytica
* *amoebicidal
se: diarrhea and GI distress
Chloroquine
- MOA (3)
- uses
- kinetics: absoprtion, distribution and to where, met
- SE (5)
MOA:
- inhibits RNA and DNA polymerase
- interferes with hemoglobin utilization by parasites–heme toxicity to parasite
- raises internal pH of parasite–>cell lysis and death
Indications:
- amebic liver dz—use with metronidazole
- malaria prophlaxis DOC
- Malaria tx: does NOT eradicate hepatic stages
- P. ovale and P. vivax— use with Primaquine
- DOC for P. falciparum –but resistance is widespread
Kinetics:
- Rapidly and completely absorbed after PO
- well distributed—> [ ]s in RBCs, liver, spleen, kidney, melanin-containing tissues, leukocytes and CNS
- met in the liver + metabolites have anti-malarial activity
SE: generally well tolerated and SE are minimal at low doses
- pruritis and rash
- GI distress
- Blurry vision and possible retinal toxicity–>do routine eye exam with prolong use
- HA
- QTc prolongation
