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Flashcards in topic 14 Deck (36):

How common is trichomonas vaginalis? How is it transmitted? What is its normal effects on women, men? What is the drug of choice?

found in 3-5% of female population of N.A.

Sexually transmitted (mother to baby as well)

asymptomatic - vast majority

symptomatic - infects vaginal epithelium and in chronic infections can invade the urethra. Vaginal pH is increased and bacteria infections can result.

In males- the urethra and prostate gland are invaded. Urethra discharge is common.

Tinidazole – drug of choice.


What is the admin, absorp, distrib of tinidazole?

orally: readily and completely absorbed

Well distributed including CSF


What is the mech of action of tinidazole

It exerts anti-protozoal activity by formation
of free radical with subsequent cell destruction


What is the primary adverse effect of tinidazole? How does it come about?

Tinidazole inhibits acetaldehyde dehydrogenase necessary to metabolize ethanol. The increased levels of acetaldehyde causes a disulfiram reaction in people that drink alcohol (nausea, vomiting, headache,abdominal cramps, and flushing.)


how common is giardia lamblia? How many of those infected are asymptomatic? Where is it primary found in the body? What is its life cycle? What are its symptoms? What is the drug of choice?

2-20% (depending on location) of population infected asymptomatically.

Found in small intestine

Life cycle-exist in environment as cysts. Passed person to person and through contaminated drinking water

90% are asymptomatic carriers

acute giardiasis includes diarrhea, gas; chronic giardiasis - diarrhea,

Tinidizole is the drug of choice


How common is entamoeba histolytica in the population? Where does it reside? How is it passed from person to person? What drug is used if it stays in the lumen? What drugs is used if it exits the lumen into tissue?

Infects 10% of general population.

Resides in large intestine

Passed through drinking water or through feces

Luminal-act only in the lumen of the bowel due to poor absorption (paramomycin)

Tissue (symptomatic-invasive systemic disease)-act systematically (Tinidazole).


What is the admin, absorp, distrib, excretion of paramomycin? What is its mech of action?

Given orally and is poorly absorbed and thus is selective for luminal trophozoites.
Excreted unchanged in feces.

Mechanism of action.

Inhibits of protein synthesis by binding to 30S ribosome.


How is the symptomatic or systemic version of entamoeba histolytica treated?


However, as it is very well absorbed in the upper intestine, it generally fails to eradicate trophozoites in the lower GI tract.

Therefore paromomycin is given.


What are the two kinds of African Trypanosomiasis (sleeping sickness)?

Etiology: There are two clinical forms: 1) a slow developing disease caused by Trypanosoma brucei gambiense and 2) a rapidly progressing disease
caused by T. b. rhodesiense


What are the early and late stages of T. b. gambiense like?

Early stage

Bite reaction
Parasitemia-found in the blood and lymph-Fever, weakness, lassitude.

Late stage found in the cerebrospinal fluid. Headaches, sleepiness (thought to be auto immune reaction to myelin) and coma. Usually take > 2 years to kill.


What is T. b. rhodesiense like?

Disease resembles gambian form except can invade the CNS within 2 weeks. Leads to terminal cardiac failure and death within several months.


What is the Mechanism of suramin? Admin? Adverse effects?


Given IV

As only a small amount of this drug crosses the blood brain barrier it is ineffective on trypanosomal infection of the brain and spinal cord.

inhibits activity of trypanosomal enzymes involved in energy metabolism, e.g., enzymes involved in glycolysis

Causes peripheral neuropathy


What Drugs are used for treatment of hemolymphatic stage trypanosomiasis (non CNS stage)? Which type is each better for?

suramin (rhodiense), pentamidine (gambiense)


What is the admin, absorp, distrib of pentamidine? What is its mechanism? Adverse effects?

Given orally it is poorly absorbed and is given by intravenous infusion administration.

It does not cross the blood brain barrier in sufficient quantities to treat infections of the brain and spinal cord.


1.) Appears to interact with DNA by binding in minor groove. Causes deletion of DNA.

2. ) Inhibits activity of topoisomerase II.

Adverse effects: Impaired renal function, damage to pancreatic islet cells-->hyperglycemia and insulin depending diabetes; not to be used in pregnancy


What two drugs are used for the CNS stage of trypanosomiasis? Which type of the disease is each better for?

Melarsoprol (both), eflornithine (gambiense, not rhodiense)


What is the admin, distrib, absorp of melarsoprol?

Well absorbed but given by IV and crosses the blood brain barrier.


What is the mech of action of melarsoprol?

1. Reacts with sulfhydryl groups of proteins thereby inactivates involved in generating ATP.

2. Melarsoprol inhibits trypanothione reductase needed to generate stores of trypanothione (similar to glutathione-reduces oxidizing agents)


What are the adverse effects of melarsoprol?

Is extremely toxic. Side effects include reactive encephalopathy (5%)-->50% fatality

Can cause severe hemolytic anemia in patients with mutation in glucose-6-phosphate dehydrogenase gene


What is the admin, absorp, distrib of eflornithine?

Given orally or by IV

Widely distributed in body including CNS.


What is the mech of action of eflornithine?

Irreversible inhibition of ornithine decarboxylase and therefore inhibits synthesis of polyamines which are required for DNA synthesis.


What are the adverse effects of eflornithine?

No severe ones


How is America Trypanosomiasis (chagas disease, trypanosoma cruzi) transmitted? How is it different than the african ones? What symptoms does it cause? What is the drug of choice?

Transmitted in feces of triatomid (Riduvid, cone nose or kissing bug) bugs.

Unlike, T.b. gambiense or Rhodesiense, T. Cruzi has an extracellular phase (trypomastigotes ) and an intracellular phase (amastigotes).

Infected individuals have fever, enlargement of the liver, spleen and heart damage (major cause of death).



What is the mech of action of Nifurtimox? Which phase of T. Cruzi does it treat?

This drug is effective in the treatment of the trypomastigote (EC, acute) but not the amastigote (IC, chronic) phases of the disease and is thought to act by producing oxygen free radicals.

The parasite appears to lack the key enzymes to inactivate these reactive species and therefore is more sensitive than the human host.


How is leischmania transmitted? What type of cells do they live in? What are the 3 types of leischmania and what are examples of each? What is the drug of choice for leishmanias?

Leishmania--transmitted by genera Phlebotomus and Lutzmyia (sand feas)

Parasite lives inside macrophages

cutaneous leishmania-L. tropica multiplies locally, after the bite producing ulcer and scar

mucocutaneous leishmania-The organisms responsible are L. braziliensis, L. mexicana and L. peruviana. Parasite found in macrophages located in mucoid tissues and lead to their destruction and hence severe deformity.

Visceral leishmaniasis (kala-azar, dumdum fever): L. donovani. They are localize and multiply in the macrophages of spleen, liver, lymph nodes, bone marrow, intestinal mucosa and other organs. Spleen and liver progressively become enlarged. Untreated disease results in death

sodium stibogluconate


What is the admin, absorption of sodium stibogluconate?

IV. It must be administered repeatedly (e.g. daily for 6 days for L. donovani infections.)


What is the mechanism for sodium stibogluconate?

Mechanism: Inhibits energy metabolism by interfering with glycolysis and fatty acid oxidation, thereby reducing the amount of ATP generated.


In general, what is the lifecycle of the plasmodium

injected during mosquito feeding

invade liver cells
Exoerythrocytic phase

invade RBCs
repeated erythrocytic phase


Which plasmodium have an erythrocytic phase and which have an exoerythrocytic phase?

Exo-erythrocytic phase
P. vivax
P. ovale

Erythrocytic phase
P. vivax
P. ovale
P. malariae
P. falciparum


Where are anti-malarial drugs located in a parasite? What is their mechanism?

parasites are in RBCs. Inside the parasite, their food vacuoles take up hemoglobin. They use the globin as their energy source, and then heme is converted to hemozoin so it doesn't become oxidative and lyse the cell.

The anti-malarial drugs target the food vacuoles. They prevent heme from being converted to hemozoin which results in lysis.


what is the absorp, admin of chloroquinone? What is the mech of action?

Orally, well absorbed.

Works in food vacuoules, prevents polymerization of heme to hemeazoin (heme polymerase)-->lysis. Also binds to DNA to prevent its template function


What are the side effects of chloroquine? Which drugs are resistant to it? How do they gain resistance?

Increase incidence of hemolysis in patients with glucose-6-dehydrogenase deficiency.

Safe in pregnancy

Resistance is gained by P. falciparum and P. vivax by only letting a little bit of the drug into the food vacuole.


What is the mechanism of action of pyrimethamine and sulfadoxine?

Both interfere in the production of folic acid and thus the production of purines, pyrimidines, methionine.


What are their side effects?

Folic acid deficiency, increased hemolysis in G6PD deficient patients, Stephen johnsons syndrome.


What is the mechanism of action, adsorp, admin of Artemether and lumefantrine (Coartem)-combination?

Pharmacokinetics. Readily absorbed following oral administration and metabolized by the liver

Mechanism of action: In the food vacuole of parasite:

Artemether contains a peroxide bridge activated by interaction with heme leading to formation of free radicals.
Lumefantrine may prevent formation of hemeazoin by inhibiting heme polymerization


How is the exoerythrocytic phase treated?

Exoerythrocytic drugs act on hepatic hypnozoites

Treat-P. ovale and P. vivax

Primaquine: acts on dormant phase in liver

Usually used along with a erythrocytic drug.


What is the mechanism of action of primaquine? What are its side effects?

Interferes with pyrimidine synthesis and mitochondrial electron transport chain.

Hemolytic anemia in patients with G6-PD deficiency, neutropenia and leukopenia I
incidence is increased with high doses of primaquine