Anti-protozoals Flashcards
What rapid-acting drugs are used to treat parasites in erythrocytic stage (blood schizontocidal agents)?
Chloroquine, Primaquine, Atremisinin
What slow-acting drugs are used to treat parasites in erythrocytic stage (blood schizontocidal agents)?
Proguanil, Pyrimethamine-sulfadoxine, Doxycycline (always in combination with fast acting)
What drugs are used to treat parasites in pre-erythrocytic stage and in latent forms known as hypnozoites (tissue schizontocidal agents)?
Primaquine
What drugs are used to treat parasites by killing gametes in the blood (gametocidal agents)?
chloroquine, primaquine, atrmisinin
What is achieved by attacking the parasite at various stages of its life cycle?
- To prevent and treat clinical attack of malaria
- To eradicate parasite from patient’s body
- To reduce human reservoir of infection – cut down transmission to mosquito
Chloroquine is Active against all species of plasmodia (gametocidal) for all except _____.
Falciparum
Chloroquine cannnot be used to prevent relapse in _____.
vivax malaria
Describe the PK of chloroquine.
It gets accumulated in several tissues (high volume of distribution, > 12 L)
Which drug has the ADR of ocular toxicity and why?
Cholorquine, selective accumulation in the retina
What is the MOA of chloroquine?
Blocks the plasmodium conversion of Fe3+-bound heme (toxic) to hemozoin (non-toxic) after digestion of Hb (occuring inside parasitic vacuole).
What is the drug of choice for the clinical cure of vivax malaria when there is no resistance?
Chloroquine
What are the uses of Chloroquine (MALARIA)?
Malaria Amoebiasis (extraintestinal / hepatic) Lepra RA (hydroxychloroquine) Infectious mononucleosis Autoimmune disorder (Discoid lupus erythematosus- DLE)
What is the triad of dose-related ADRs with quinine?
- Cinchonism (tinnitus, high-tone deafness, visual disturbances, headache, dysphoria, nausea, vomiting, and postural hypotension)
- Hypoglycemia
- Hypotension (precautions)
What are two severe ADRs of quinine?
Prolonged Q-T
G-6PD deficiency hemolysis
What is the MOA of artemisinin?
- Interact with heme in the parasite, release of highly reactive free radicals
- Bind to membrane proteins; damages endoplasmic reticulum (inhibits parasite Ca2+ ATPase)
- Lysis of parasite
What are the oral forms of artemisinin?
Dihydro-artemisinin, artesunate, artemether
Artemisinin is drug of choice for what two conditions?
Cerebral malaria and complicated malaria
*****If give anti-folate with another bone marrow suppression drug then what ADR can occur?
Neutropenia
What is the MOA of Sulfadoxine?
Structural analogs of PABA-compete with PABA for dihydropteroate synthetase (first step)
What is the MOA of Pyrimethamine?
Inhibits folate biosynthesis –high affinity inhibition of plasmodial DHFR / Dihydrofolate reductase (third step)
What combination of anti-folates is used for treatment of chloroquine resistant P. falciparum and why?
sulfadoxine+ pyrimethamine acts as slow acting blood schizonticidal and provide sequential blockade
Which anti-folate is used for drug sensitive P. falciparum and P. vivax and what is its MOA?
Proguanil, inhibits dihydrofolate reductase
What is the MOA of atovaquone?
inhibits malarial cytochrome bc1 in the mitochondrial electron transport chain→ disrupts mitochondrial membrane potential
What are the targets of atovaquone?
both tissue and RBC schizonts
What combination of anti-protozoals is used for for treatment of uncomplicated malaria and chemoprophylaxis, alternate therapy for P. jiroveci infection( lower efficacy)?
Malarone (atovaquone + proguanil)
What is the MOA of primaquine?
Produce ROS causing cellular oxidative damage
What stage of parasite does primaquine work on and what kind of activity does it have?
Tissue schizontocide for all 4 species of plasmodia (primary and latent forms, i.e. hypnozites), marked gametocidal activity
Which anti-protozoal is used as a radical cure (to prevent relapse by eliminating hypnozoites) given concurrently or after clinical cure (after G6PD status known)?
Primaquine
How do you give primaquine for P. vivax?
Once a day for 14 days
How do you give primaquine for P. falciparum and what is its importance?
Radical cure (to prevent relapse by eliminating hypnozoites) given concurrently or after clinical cure (after G6PD status known)
The combination of _____ and _____ is an alternative regimen for the treatment of pneumocystosis (caused by Pneumocystis jiroveci)?
clindamycin, primaquine
When is primaquine used in contradicted and why?
G6PD deficiency, pregnancy and infants, granulocytopenia, concurrently with BM depressants, bc rarely ADR / can cause BM depression
***** Interrupt the G6PD enzyme assay results: <20% = _____, 40%-60% = _____, 70% - 90% = _____. When can you not use primaquine?
normal, mild G6PD/heterozygous, severe G6PD = and CANNOT give drug
What is the treatment of malaria caused by P. vivax?
Chloroquine for clinical cure + Primaquine (14 days) to prevent relapse (radical cure)
What is meant by the term “radical cure” when treating malaria?
attack exo-erythrocytic stage (hypnozoite) to achieve total eradication of parasite from patient’s body (tissue form)
*****What is the treatment used as a clinical cure for malaria caused by P. falciparum?
Artemisinin Combination Therapy + + primaquine (single dose -to prevent transmission of malaria only)–> choose the answer ACT as Rx even if primaquine is there!!
What is the treatment for severe (complicated) malaria?
Artemisinin derivatives –or- Quinine, parenteral route
How do you treat malaria in pregnancy?
1st trimester : Quinine for 7 days, followed by area specific ACT in 2nd and 3rd trimester OR Clindamycin–> remember do NOT give primaquine
Term for Use of drugs to prevent infection, rather than for treatment of malaria
Chemoprophylaxis
When is chemoprophylaxis recommended?
For travellers, migrant workers and military personnel exposed to malaria in highly endemic areas
Which anti-malarial is not recommended as prophylaxis in highly endemic areas due to high recurrence rate and chance of resistance?
Primaquine
What anti-malarial is DOC for chemoprophylaxis on trips > 6 wks. long and what dose would you give?
Mefloquine, Once a week, started 3-4 weeks earlier, continued for 4 weeks after return
What anti-malarial is DOC for chemoprophylaxis on trips 1 wk. to 6 wks. long and what dose would you give?
Doxocycline, Once a day, started 1-2 days earlier, continued for 4 weeks after return
What anti-malarial is DOC for chemoprophylaxis on trips < 7 days long and what dose would you give?
Atovaquone/proguanil (Malarone), Once a day, started 1-2 days earlier, continued for 7 days after trip
What is the drug therapy for Chloroquine sensitive P. falciparum and malaria?
Chloroquine
What is the drug therapy for P. Vivax and ovale?
Chloroquine, Primaquine
What is the drug therapy for uncomplicated infections with chloroquine resistant P falciparum?
Coartem (Artemether+lumefantrine)
What is the alternative drug therapy for uncomplicated infections with chloroquine resistant P falciparum?
Malarone OR Mefloquine OR Quinine sulfate
What is the drug therapy for severe or complicated infections with P falciparum?
Artesunate; follow with doxycycline or clindamycin or coartem or mefloquine
What is the alternative drug therapy for severe or complicated infections with P falciparum?
Artemether; follow with artesunate OR Quinidine gluconate OR Quinine dihydrochloride
What are the luminal amoebicides act on the parasite in the lumen of the bowel?
tetracyclines and iodoquinol
What are the systemic or tissue amoebicides teffective against amoebas in the intestinal wall and liver?
Metronidazole, Tinidazole, chloroquine (know these!)
What are the three main reasion chloroquine is used in combination with metronidazole and diloxanide furoate?
- To treat and prevent amebic liver abscesses
- Eliminates trophozoites in liver abscesses
- Not useful in treating luminal amebiasis
What are the ADRs of Metronidazole?
- bitter metallic taste
- disulfiram-like effect
- potentiates anticoagulant effect of warfarin causing bleeding
- potentiates lithium toxicity (polyuria, dilute urine, and can clear faster so have mania/psychotic symptoms manifest sooner)
Metonidazole is used for _____ and _____.
Giardiasis (Giardia lamblia), Trichomoniasis (Trichomonas vaginalis)
What is the preferred combination to treat Toxoplasmosis (Toxoplasma gondii)?
Pyrimethamine and Sulfadiazine +folinic acid
When a patient is diagnosed with _____, both sexual partners are treated simultaneously with Metronidazole.
Trichomoniasis (Trichomonas vaginalis)
What are the ADRs of the broad spectrum anti-protozoal pentamidine used in Pneumocystosis (PCP), sleeping sickness (African trypanosomiasis), and leishmaniasis?
Hypoglycemia (5-7 days after use due to insulin release) for couple weeks, followed by hyperglycemia insulin resistance in some cases (because of acute pancreatitis)
Nephrotoxic
Acute pancreatitis
*****How would you treat a traveling soldier with non-healing ulcer on forearms and / or face (any exposed area) transferred by a sandfly?
Sodium stibogluconate (pentavalent antimonials prodrug to treat Leishmaniasis)
Sleeping sickness aka African trypanosomiasis is caused by _____ transmitted by the _____.
Trypanosoma brucei, tsetse fly
What is the treatment for the first stage of sleeping sickness aka African trypanosomiasis in which there is hemolysis and lymphonode enlargement?
suramin, eflornithine (ornithine decarboxylase inhibitor)
What is the treatment for the second / late stage of sleeping sickness aka African trypanosomiasis in which there is CNS involvement and sleeping disturbances?
melarsoprol (arsenical, arsenic use to be used for bed bugs)
