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
list drugs used in tx of malaria (5)
- Primaquine
- Chloroquine
- Atovaqone-proguanil
- Mefloquine
- Quinine
Primaquine
- uses (DOC for?) Not used for?
- MOA
- SE
- pregnancy
INDS:
- DOC–eradication of liver forms of plasomida
- DOC for prophylaxis for sensitive areas
- relapse of P. vivax and P. ovale (which remian in liver)
BUT CANNOT BE USED AS MONOTHERAPY because not used for erythrocytic stage
**usually combo with Chloroquine/other x14 days
MOA:
*disrupting plasmodium mitochondiral processes
SE:
- gen well tolerated
- drug-induced hemolytic anemia in G6PD–have to test PT b4 initiating tx
- abdominal discomfort
- methemoglobinemia
*contra in preg
Mefloquine -related to what other drug _MOA -kinetics: t 1/2, how to take it, concentrates where, -pregnnacy and kids
*related to quinine
USES:
- prophylaxis of ALL plasmodia (CDC recc to use this when chloroquine resistance areas)
- used with artesunate
MOA:
*poorly understood
Kinetics:
- T 1/2= long because it enters enterohepatic circulation
- Concentrates in tissues
Needs weekly dosing
take with meals + water
SE:
- Neuropsychiatric–>why it is reserved for use when other agents cannot be used
- EKG changes and arrest when taken with Quinine or Quinidine
Safe in pregnancy and kids
Suramin
- uses
- route of admin
- BBB?
early stage (w/o CNS involvement) of african sleeping sickness—- casued by Trpanosomiasis brucei rhodesinse
route: HAS TO BE IV because binds to plasma proteins
does not penetrate BBB–why its used for the NON CNS invovlement stage
SE: pretty infrequent
- nauea/vom
- shock
- LOC
- acute urticaria
- blepharitis
- neuro–>paresthesias, photophobia, hyperesthesia of hands/feet
Melosoprol
- uses
- route of admin
- half life
- excretion
- penetration
- SE
IV–slow
**can be irritating to vessels
Late stages of african sleeping sickness–>T. brucei rhodesiense
WITH CNS INVOLVEMENT
- good CNS penetration
- short half life
- rapidly excreted in urine
SE:
- can cause CNS toxicity– encephalopathy***, periph neruopathy,
- HTN
- hepatoxicity
- albumineria
- hemolytic anemia can occur with G6PD PT
MOA:
*host body will oxidize the drug into a nontoxic form of arsenic
Benznidazole
- uses
- se
chagas dz
better tolerated drug
BUT treatment with this drug is limited due to toxicity
SE:
- dermatitis
- peripher neuropathy
- insomina
- anorexia
Nifurtimox
-uses
uses: Chagas DZ
* has more toxic SE vs Benznidazole
SE:
- hypersen rxn—anaphy to dermatitis
- GI problems that are severe enough to cause wt loss
- periph neruopathy
- HA
- dizziness
Pentamidine
- uses
- routes
- MOA
- CNS penetration?
USES
- **Pneumocystis jirvovecci—-alternative for PT with sulfa allergy
- Leishmaniasis
ROUTES: IV, IM, Neb (only for prophylaxis)
tx of PCP is IV or IM
DOES NOT enter CNS—so cannot treat late trypanosomiasis
SE:
- reversible renal dysfunction
- life threatening hypoglycemia
- hypoK
- hypotension
- pancreatitis
- cardiac arrhythmias
