Antiparasitic Questions Flashcards
What percent of the world’s population is chronically infected with parasites?
50%
How are parasites causing human disease categorized?
Two main categories
- unicellular protozoa
- multicellular helminthes
How are protozoa categorized?
Have many subgroups but can be categorized into:
- intestinal
- primarily extraintestinal pathogens
How are helminthes subdivided?
- nematodes (roundworms)
- trematodes (flukes)
- cestodes (tapeworms)
What two other organisms (technically not considered parasites) are susceptible to antiparasitics?
- Pneumocystis jirovecii (technically a fungus)
- Sarcoptes scabiei (scabies mite; technically an Arachnid)
What is plasmodium (malaria)?
Extraintestinal protozoa
What is toxoplasma?
Extraintestinal protozoa
What is trypansoma?
Extraintestinal protozoa
What is entamoeba?
Intestinal protozoa
What is giardia?
Intestinal protozoa
What is cryptosporidium?
Intestinal protozoa
What is ascaris?
Nematode
What is strongyloides?
Nematode
What is schistosoma?
Trematode
What is echinococcus?
Cestode
What is taenia?
Cestode
What is pneumocystis?
Fungus
What is scabies?
Ectoparasite
Name the quinolines?
- Chloroquine
- Mefloquine
- Quinidine
- Quinine
- Primaquine
- amodiaquine
- hydroxychloroquine
From what tree are quinoline agents derived?
Cinchona tree bark
- imported from Peru
- used to treat fever in malarious areas of Europe dating back to the 17th century
- quinine was the primary component in the bark
What determines differences in activity for the quinolines?
- species of Plasmodium
- geographic area
What is the MOA of quinolines?
MOA on parasites are incompetent understood
What is the MOA of quinine, quinidine, and chloroquine?
Appear to interfere with the ability of the malaria parasite to detoxify hemoglobin metabolites
What is the MOA of primaquine?
Appears to affect parasitic mitochondrial function
What protozoa are quinolines active against?
Activity variable by region
- Plasmodium falciparum
- P. malariae
- P. ovale
- P. vivax
What fungus is primaquine active against?
P. jirovecii
Describe quinoline CV toxicity.
Dose related CV toxicity
- QT interval prolongation
- hypotension
- potentially fatal ventricular arrhythmias
What class of anti-arrhythmic is quinidine?
Class IA
- used therapeutically in the treatment of some arrhythmias
- can be proarrhythmic
Wth which quinoline are CV effects most likely?
IV quinidine
Wth which quinolines are CV effects less common?
- quinine
- mefloquine
- chloroquine
Wth which quinoline are CV effects rare?
Primaquine
Which quinoline can cause hematologic effects.
Primaquine
- can cause hemolysis in patients deficient in glucose-6-phosphate dehydrogenase (G6PD)
- testing for G6PD deficiency is required before use
Which quinolines can cause metabolic effects.
Quinidine and quinine
- profound hypoglycemia
- resulting from stimulated release of insulin
Which quinoline can cause psychiatric effects.
Mefloquine
- associated with a range of psychiatric disturbances
- well tolerated by the vast majority patients but certain patients may experience them
- insomnia
- vivid dreams
- mood swings
- depression
- psychosis
- suicide
What patients should avoid taking mefloquine?
History of psychiatric issues
-includes depression
Which quinoline can cause cinchonism?
Quinine
- common in patients receiving therapeutic doses
- tinnitus
- headache
- nausea
- visual disturbances
- can lead to discontinuation of therapy due to intolerance
- resolves after drug discontinuation
Which quinoline is available as IV form in the US?
Quinidine
-used in combination regimens for treatment of severe malaria
How should IV quinidine be monitored?
Continuous monitoring of
- BP
- ECG
Serial monitoring
-blood glucose
How does renal failure affect IV quinidine dosing?
Dosing is altered
-not uncommon in severe malaria
What makes primaquine special compared to other antimalarials?
Active against the “hypnozoite” forms of P. vivax and P. ovale
- can lay dormant in the liver and cause relapsing infections
- 2 week course of primaquine is added when these species is documented
What is chloroquine good for?
- treatment of uncomplicated malaria acquired in chloroquine sensitive areas (only a few regions)
- prophylaxis against malaria in travelers to those regions
What is mefloquine good for?
- treatment of uncomplicated malaria acquired in mefloquine sensitive areas (most of the world except Southeast Asia)
- prophylaxis against malaria in travelers to those regions
What is quinine/quinidine good for?
- treatment of severe malaria (quinidine) in combination with
- doxycycline
or
-tetracycline
or
- clindamycin
- not used for prophylaxis
What is primaquine good for?
- treatment of uncomplicated malaria due to P. vivax or P. ovale in combination with a second agent
- prophylaxis against malaria in travelers where P. vivax is the principal species
- in combination with clindamycin
- treatment of mild to moderate Pneumocystis pneumonia
What is atovaquone?
Antiparasitic
-activity against several important protozoans
What is Malarone?
Atovaquone in combination with proguanil
-enhanced activity against the malaria parasite
How is atovaquone tolerability compared to other drugs?
Better tolerated
What limits atovaquone use?
- lack of IV formulation (for severe disease)
- high cost
- somewhat lower efficacy (for Pneumocystis disease)
What is the MOA of atovaquone?
Appears to interfere with electron transport in the parasitic mitochondria
What fungus is atovaquone active against?
P. jirovecii
What protozoa is atovaquone active against?
- Plasmodium species
- Toxoplamsa gondii
- Babesia species
How is atovaquone tolerated?
Very well tolerated
What are the most common adverse effects with atovaquone?
GI
- nausea/vomiting
- diarrhea
- abdominal pain
How is atovaquone available?
Suspension
How is Malarone available?
Tablet
How is atovaquone and Malarone bioavailability?
Low with both
-enhanced substantially when given with food (especially high fat meals)
How active is atovaquone in treating mild to moderate Pneumocystis pneumonia in patients intolerant of TMP/SMX?
- slightly less effective than comparators (dapsone or pentamidine)
- better tolerated
- lead to similar overall success rates
When should atovaquone not be used against Pneumocystis?
- severe Pneumocystis pneumonia
- patients whose GI absorption is thought to be poor
Why is Malarone favorable for malaria prophylaxis for travelers?
- highly effective
- well tolerated
- active against chloroquine resistant Plasmodium
What is the timeframe for Malarone prophylactic use?
- start 1-2 days before travel
- take while in the malaria-endemic area
- continue for 7 days after return
What is the timeframe for many other antimalarials for prophylactic use?
- start 2 weeks before travel
- continue for 4 weeks afterward
What is atovaquone good for?
- treatment of mild to moderate Pneumocystis pneumonia
- prophylaxis against Pneumocystis in patients intolerant of first line therapy
What is Malarone good for?
- treatment of uncomplicated malaria
- prophylaxis against malaria
How should patients take atovaquone?
- with food (or at least a glass of milk)
- bioavailability is increased 5x when administered with food
Name the benzimidazoles.
- albendazole
- mebendazole (no longer available in US)
- thiabendazole (no longer available in US)
What are benzimidazoles used for?
Primarily for helminthes (worms)
- range from common pinworms to pathogens causing massive cystic lesions in the brain
- most intestinal worm infections can be cured with a single dose
- tissue invasive diseases require prolonged courses
What is the MOA of benzimidazoles?
Interfere with elongation of the microtubules responsible for parasitic cellular structure
-leads to disruption of growth and division
What nematodes (roundworms) are benzimidazoles active against?
- Ascaris lumbricoides (roundworm)
- Enterobius vermicularis (pinworm)
- Necator americanus (hookworm)
- Strongyloides stercoralis (threadworm)
What cestodes (tapeworms) are benzimidazoles active against?
- Echinococcus (liver abscess)
- Taenia solium (neurocysticercosis)
How is single dose therapy of albendazole for intestinal worm infections tolerated?
Very well tolerated
What adverse effects do multi dose regimens of albendazole have?
- primarily GI
- hepatotoxicity (rare)
- neutropenia (rare)
Which benzimidazole is most toxic?
Thiabendazole
-can cause CNS adverse effects
Can benzimidazoles be used in pregnancy?
Should generally be avoided
-some data suggest may be safe after first trimester
Are benzimidazoles affected by drug interactions?
- appear to be substrates of the P450 system
- strong inducers (rifampin, phenytoin) may lower serum levels
How is oral absorption of albendazole?
Limited
- generally does not pose a problem for treatment of intestinal nematode infections (drug interactions not a concern)
- for systemic infections, be aware of interactions
What are benzimidazoles good for?
- single dose therapy of most intestinal nematode infections
- alternative for treatment of Strongyloides infection
- treatment for tissue invasive Echinococcus or Taenia infection
What can drug induced killing of some parasitic infections cause?
Releases antigens that can cause allergic reactions
-corticosteroids are sometimes administered to mitigate these effects
What is the primary alternative to TMP/SMX for patients with Pneumocystis pneumonia?
Pentamidine
-Pneumocystis was once an extremely common cause of severe pneumonia in HIV patients before effective antiretrovirals
How can pentamidine be administered?
IV or inhalation
-proper route depends on indication
What is the MOA of pentamidine?
Appears to bind to and disrupt function of tRNA
-results in inhibition of protein synthesis
What fungus is pentamidine active against?
P. jirovecii
What protozoa is pentamidine active against?
- Trypanosoma
- Leishmania
What are the categories of adverse effects of IV pentamidine?
- CV
- metabolic
- renal
- respiratory
Describe the CV effects of IV pentamidine.
- hypotension with rapid infusion (infuse over at least an hour)
- cases of QT prolongation with ventricular arrhythmia have been reported
Describe the metabolic effects of IV pentamidine.
Toxic to the pancreas
- dysglycemias in up to 25% of patients
- other manifestations of pancreatitis may occur
Describe pentamidine induced dysglycemia?
- initially may manifest as hypoglycemia (pentamidine induced pancreatic injury causes release of insulin from islet cells)
- continuing injury can cause decrease in pancreatic function (hypoinsulinemia and hyperglycemia)
- continued use may lead to irreversible damage (leaving patients with DM)
Describe IV pentamidine renal effects.
Nephrotoxicity is common
-generally reversible upon drug discontinuation
What electrolyte disturbances can IV pentamidine cause?
- hypokalemia
- hypocalcemia
Describe IV pentamidine respiratory effects.
Inhalation administration may induce bronchoconstriction (especially in asthma patients)
-pretreatment with an inhaled bronchodilator may lessen these effects
How does pentamidine compare to SMX/TMP for Pneumocystis pneumonia?
About equal in efficacy
-only half could tolerate a full course of IV pentamidine without stopping or decreasing the dose
What are considerations when giving IV pentamidine?
Careful monitoring
- ECG
- metabolic panel
Supportive care interventions
- electrolyte replacement
- glucose
- insulin
Is dosage adjustment for pentamidine in renal sufficiency required?
Recommended
How often is inhaled pentamidine given for prophylaxis against Pneumocystis pneumonia?
- once monthly
- reasonable efficacy as 2nd line agent
What are the downsides to giving inhaled pentamidine for prophylaxis?
- cases of extrapulmonary Pneumocystis infections have been reported
- does not protect against Toxoplasma disease or bacterial pneumonia like TMP/SMX
What is IV pentamidine used for?
- alternative for treatment of severe Pneumocystis pneumonia
- alternative for treatment of leishmaniasis and trypanosomiasis
What is inhaled pentamidine used for?
-alternative for prophylaxis against Pneumocystis pneumonia
What drugs may a patient on pentamidine also be in on that could exacerbate its toxicities?
- insulin
- furosemide
- aminoglycosides
- antiarrhymthics
What is ivermectin active against?
- scabies
- Norwegian scabies (highly contagious)
- Strongyloides hyperinfection syndrome (increasingly recognized cause of life threatening illness in immunocompromised patients)
- several diseases endemic in tropical settings
Which tropical diseases is ivermectin active against?
- river blindness
- strongylodiasis (infrequent in US)
- cutaneous larva migrans (infrequent in US)
What is the MOA of ivermectin?
Binds to the parasitic neuromuscular junction
- causes muscular paralysis of the parasite
- parasite dies directly from the effects or starvation
What ectoparasites is ivermectin active against?
- Sarcoptes scabiei (scabies mite)
- Pediculus humanus (lice)
What nematodes (roundworms) is ivermectin active against?
- Onchocerca volvulus (river blindness)
- Strongyloides stercoralis (strongylodiasis)
- Ancylostoma braziliense (cutaneous larva migrans)
- other nematodes
How is ivermectin tolerated when used for treatment of scabies?
Very well tolerated
How is ivermectin tolerated when used for management of nematode infections in endemic settings?
Severe adverse reactions
- fever
- myalgia
- hypotension
- thought to be a result of the host’s immune response to antigens released from killed parasites
- more severe in patients with higher worm burdens
- resolve soon after drug administration
What is ivermectin used as an alternative for?
- alternative to topical permethrin for scabies
- to topicals for treatment of head or body louse infestation
- treatment of Ancylostoma infections
What is ivermectin a drug of choice for?
- Strongyloides
- Onchocerca
How is ivermectin dosed for ectoparasitic (scabies or lice) infestation?
Administer as 2 doses
- 1 week apart
- only giving a single dose increases the risk of relapse
