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Pharm Antiprotozoal
KYCOM Block 10
82
Pharmacology
Graduate
09/29/2013

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Cards

Term
why do antiprotozoal drugs cause more side effects, where are they usualy at? (4)
Definition
Protozoa are eukaryotes and have metabolic processes closer to humans so drugs have more toxic effects

Increased in cells with high metabolic activity like kidney, neurons, intestinal, and stem cells
Term
what is the most common ameoba pathogen and the disease it causes
Definition
E. histolitica
amebiasis (amebic dysentery)
Term
what are the three categories of amebocides, what distinguishes them
Definition
mixed: effective in lumen and systemic, concentration too low for single drug treatment

luminal: act on parasite in lumen of bowel

systemic: act on parasite in intestine wall and liver
Term
what are the three antiameoba drugs and their category
Definition
mixed: metronidazole
luminal: diloxanide furolate
systemic: chloroquine
Term
what transmits malaria
Definition
female anopheles mosquito
Term
what are the 4 types of malaria, what is the their severity and prevelence
Definition
plasmodium falciparum: severe, common
P. vivax: mild, common
P. malariae: mild very common
P. ovale: mild, rare
Term
what categories of drugs are used to treat malaria (2)
Definition
tissue schizoniticides
blood schizoniticides
Term
what are the tissue schizoniticides
Definition
primaquine
Term
what are the blood schizoniticides (3)
Definition
chloroquine
quinine
mefloquine
Term
what two diseases do trypanosomiasis cause
Definition
african sleeping sickness
american sleeping sickness (Chagas')
Term
what microbes cause african sleeping sickness (2)
Definition
T. bruceo gambiense
T. bruci rhodinese
Term
what microbe causes american sleeping sickness
Definition
T. cruzi
Term
what is the treatment for trypanosomiasis (3)
Definition
melarsoprol
pentamidine
isethionate
nifurtimox
Term
how is leshmianisis transmitted
Definition
animal to human by bite of sand flies
Term
what are the three types of leshimaniasis
Definition
cutaneous
mucocutaneous
visceral
Term
what is the treatment for leshimaniasis
Definition
sodium sitbogluconate
Term
what is the cause of toxoplasmosis
Definition
Toxoplasma gondii
Term
what is the transmission of toxoplasmosis gondii (2)
Definition
raw meat or oocytes shed from cats
Term
what is the treatment of toxoplasmosis gondii
Definition
pyrimethamine
Term
what is the most commonly diagnosed intestinal parasite in the US
Definition
giardia lamblia
Term
how is giardia transmitted
Definition
contaminated water
Term
how is giardia treated
Definition
metronidazole
Term
what are the two forms of E. histolytica, where are they located
Definition
Cysts: survive outside the body

Labile: invasive trophozoites that cannot live outside the body
Term
how is E. histolica transferred, where does it grow, how does it cause infection
Definition
Cysts ingested through feces contamination and pass to intestines

Trophozoites are born and invade and ulcerate the mucosa and feed on intestinal bacteria

As they increase in numbers they are able to invade systemically

As they migrate to the rectum they return to cyst form and are excreted in feces
Term
how is E. histolitca diagnosed
Definition
E. histolytica in fresh feces
Term
what are the signs of P. falciparum (5)
Definition
persistent high fever
orthostatic hypotension
erythrocytosis (swollen limbs)
capillary obstructiondeath
Term
why is P. falciprum dangerous (3)
Definition
it can infect RBC of any age
increased drug resistance
increased insectacide resistance
Term
what is the main clinical concern for P. vivax
Definition
may remain in the liver after the blood part of the disease is elminated
Term
what is the main clinical concern for P. ovale
Definition
may remain in the liver after the blood part of the disease is elminated
Term
how is trypanosomiasis acquired, where does it go in the body, how does it cause pathoology, what are the signs
Definition
Initially live and grow in the blood

Invade CNS and cause inflammation of the brain and spinal cord

Produces lethargy and continuous sleep
Term
metronidazole: MOA
Definition
ferredoxin like, low redox, e- transport chains occur in anaerobic abeobe making ROS.

nitro group of drug accepts e- and forms reduced cytotoxic compounds that bind to proteins and DNA causing cell death
Term
diloxanide furolate: MOA
Definition
abebicidal, unknown
Term
chloroquine: MOA (4 parts)
Definition
1. decreases DNA synthesis but disrupting tertiary structure of DNA

2. alkalinization of food vacoule: tops Hb digestion of the parasite by going into food vacoule and picking up a protein and making the food basic

3. interferes with heme polymerase: parasites eat Hb to get AA and Fe but this makes soluble Hb which is toxic so it uses heme polymerase and turns the Hb into hemozoin and puts it away in its food vacoule.

4. binds ferriprotoprophyrin iX damaging membrane causing lysis of the parasite and RBC
Term
primaquine: MOA
Definition
intermediates act as oxidants which cause hemolysis and methemoglobenmia toxicities
Term
quinine: MOA (3 parts)
Definition
inhibit heme polymerase

affect DNA synthesis

damage the membrane
Term
mefloquine: MOA
Definition
damage parasite membrane
Term
melarsprol: MOA
Definition
reacts with sulfhydryl inducing enzymes in organism and host
Term
pentamide isethionate: MOA
Definition
binds to parasite DnA and stops RNA/DNA/phospholipid/protein synthesis in parasite
Term
nufutrimox: MOA
Definition
undergoes reduction so it has a free e- to attack O2 forming superoxide, hydeoxyl, and H2O2 raicals. Organism dosent have catalase so it kills it
Term
sodium sitbogluconate: MOA
Definition
reduced to trivalent antiomy for activity

inhibits phosphofructokinase stopping glycolysis
Term
pyrimethamine: MOA
Definition
stops diydrofolate reductase at a low enough concentration to not inhibit it in the host

this deprives it of tetrahydrofolate so it cant make purines and pyrimidines
Term
chloroquine resistance
Definition
some P. falciprum has become resistant
Term
metronidazole resistance
Definition
some trichomonas have become resistant
Term
metronidazole: side effects (7)
Definition
GI: nausea, vomiting, cramp

metalic taste
oral moniliasis

disulfiram like effect

rare CNS: numbness upon drug discontinuation
Term
diloxanide fulorate: side effects (3)
Definition
mild flatulence

dryness of the mouth

puritus
Term
chloroquine: side effects (3)
Definition
ECG changes - quinidine effect

chronic Tx: discoloration of nail beds, visual disturbances
Term
primaquine: side effects (3)
Definition
GI

drug induced hemolytic anemia in people with low G6PDH

rare blood dyscrasia in patients with lupus
Term
quinine: side effects (7)
Definition
cinchonism: nausea, vomiting, tinnitus, vertigo

discontiune for positive coombs test for hemolytic anemia

potentiation of neuromuscular blocking agents (surgery)

elevation of digoxin levels
Term
mefloquine: side effects (3)
Definition
dizzy, disorientation, hallucinations (caution to SCUBA divers), neurotic and psychotic stuff
Term
melarsoprol: side effects (1)
Definition
CNS: encephalopathy may appear soon after therapy. Usually subsides, can be fatal
Term
pentamide isethionate: side effects (3)
Definition
renal dysfunction

hypotension

toxic to B cells of pancreas
Term
nifurtimox: side effects (3)
Definition
anaphylaxis

delayed hypersensitivity

peripherial neuropathy
Term
sodium sitbogluconate: side effects (1)
Definition
cardiac arrhythmia
Term
pyrimethamine: side effects (2)
Definition
megaloblastic anemia: reversable with leuconvorin

hypersensitivity (can be severe)
Term
metronidazole: administration, absorption
Definition
oral
rapid and complete
Term
diloxanide furolate: administration, absorption (and its significance)
Definition
90% absorbed, but the unabsorbed part is the amebocide
Term
chloroquine: administration
Definition
oral
Term
primaquine: administration
Definition
oral
Term
melarsoprol: administration
Definition
IV
Term
pentamide isethionate: administration methods, why not the others
Definition
IM or aerosol

Avoid IV: tachycardia, decrease in BP
Term
sodium sitboqluconate: asministration
Definition
paraentral
Term
metronidazole: how is it metabolized (2), what can enhance this (1), what can increase the half life (1)
Definition
hepatic oxidation of the side chain by oxidase and glucuronidation (accumulates in hepatic disease)

enhanced by phenobarbital

cimetidine increases half life (heart burn)
Term
chloroquine: metabolism
Definition
some metabolic products retain antimalarial activity
Term
primaquine: metabolism
Definition
rapidly oxidized to many other compounds
Term
primaquine: distribution and its significance
Definition
can get to the liver to get P. vivax and P. ovale but does not concentrate anywhere in particular
Term
quinine: distribution
Definition
widly distributed
Term
quinine: excretion
Definition
excretion decreased due to alkalinization of the urine
Term
what antiprotozoa has the longest half life how long is it, who is the runner up
Definition
mefloquine
long half life (17d)

pentamide isethionate
Term
what antiprotozoa enters the CNS
Definition
melarsoprol
Term
melarsoprol: metabolism
Definition
host oxidizes non-toxic pentavalent arsenic compoind
Term
what is pyrmithamine used to
Definition
T. gondii
Term
what is sodium sitboglyconate used for
Definition
leishmaniasis
Term
what is nifurtumox used for
Definition
acute T. cruzi infection, chronic stage treatment results are variable (drug is supressive not curative)
Term
what is pentamide isethionate used for (2)
Definition
T. brucei gambinese in hematological stage

Pneymocystis carinii
Term
what is melarsoprol used for
Definition
drug of choice: late stages with CNS involvement for gambinense and rhodesiense
Term
what is mefloquine used for (2)
Definition
prophylaxis for chloroquine resistant malaria (also doxycycline)

treatment for chloroquine resistant malaria
Term
what is quinine used for (2)
Definition
reserved for resistant strains

treatment for chloroquine resistant malaria
Term
what is primaquine used for (5)
Definition
kills…
*primary exoerythrocytic P. falciparum and P. vivax
*secondary exoerythrocytic forms of P. vivax and P. ovale (in liver)
*sexual forms of all plasmodia are destoried in blood or prevented from maturing
*little activity on erythrocytic schizonts so often used in combo with blood schizoniticide
Term
what is metronidazole used for (3), how is it used
Definition
E. histolitica
Giardia lamblia
Trichomonas vaginalis

usually combined with a luminal ameboside because it is rapidly absorbed
Term
what is diloxanide furolate used for (2)
Definition
asymptomatic passers of cysts

intestinal amebiasis
Term
what is chloroquine used for (4)
Definition
use with metronidazole and diloaxnide to treat and preent liver abscesses

drug of choice forerythrocytic P. falciparum

prophylaxis for chloroquine sensitive malaria

treatment for chloroquine sensitive acute malaria
Term
what drug has to be gotten from the CDC
Definition
diloxanide furolate
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