Antiprotozoal drugs Flashcards
Only one cycle of liver cell invasion and multiplication
occurs, and liver infection ceases spontaneously in
less than 4 weeks
PLASMODIUM FALCIPARUM AND P.
MALARIAE INFECTIONS
Eradication of both erythrocytic and hepatic parasites
is required to cure these infections and usually
requires two or more drugs
PLASMODIUM VIVAX AND P. OVALE
INFECTIONS
§ For eradication of vivax and ovale, it is important to
give a drug that would eradicate dormant liver form
such as
primaquine and tafenoquine
eliminate developing
dormant liver forms seen in P. ovale and vivax
Tissue schizonticides
act on erythrocytic parasite
blood schizonticides
kill sexual stages and prevent
transmission to mosquitoes
Gametocides
- eliminate both hepatic and erythrocytic
stages
Radial cure
drugs that prevent heme detoxification
Quinine, chloroquine, mefloquine, Primaquine
Folic acid synthesis inhibitors
Pyrimethamine, Proguanil, Dapsone, Sulfadoxin
Protein Synthesis Inhibitors
Doxycycline
Clindamycin
Inhibit mitochondrial function
Atovaquone,
Tafenoquines
Generate free radicals and damages protein and lipids
Artemisinin
active against asexual
blood stages; will treat/prevent clinically symptomatic
malaria since signs and symptoms of malaria occur
where there is erythrocytic invasion of malaria
CAMPQST (Chloroquine, Artemisinin,
Mefloquine, Pyrimethamine, Quinine/Quinidine,
Sulfadoxin, Tetracyline)
target asexual
erythrocytic form and liver stages of falciparum. They
shorten several days required for post op
chemoprophylaxis
Atovaquone
Proguanil
effective against
primary and latent liver stages as well as gametocytes;
Primaquine and tafenoquine
§ They are optimized for the treatment of severe falciparum
§ They are effective against asexual erythrocytic stage
of vivax
Artemisinin and its derivatives
generate free radicals
that alkylate and oxidize macromolecules in the parasite
Artemisinin
Toxicity and contraindications (Artemisinin)
- inc transaminase levels
- decreases in reticulocyte count and neutrophil counts
- x for 1st trimester of pregnancy
recommended during the first trimesters of pregnancy
Quinine plus clindamcyin or Mefloquine
recommended for the tx of severe malaria during all stages of pregnancy
IV artesunate
is well absorbed orally without
important food effect. It has excellent efficacy
against falciparum and vivax, It is well tolerated
Pyronaridine
toxicities of artesunate
hepatic and agranulocytosis
ACT with longest half-life: 5 weeks
Piperaquine - Dihydroartemisnin (artekin)
o It acts by concentrating in parasite food
vacuoles à preventing the biocrystallization of the hemoglobin
breakdown product, heme, into hemozoin à
eliciting parasite toxicity due to the buildup
of free heme
Chloroquine
Drug of choice for treatment and chemoprophylaxis of
falciparum malaria
- synthetic 4-aminoquinolone
Chloroquine
Chloroquine
Rapidly and almost completely absorbed
from the GIT, reaches maximum plasma
concentration in about _ hrs
3 hrs
Chloroquine resistance can be reversed by
verapamil, desipramine, chlorphreniramine
most common AE of chloroquine
Pruritus
Blood AE of chloroquine
Hemolysis g6pd
agranulocytosis
AE chloroquine long term administration
Irreversible ototoxicity, retinopathy,
myopathy, peripheral neuropathy
Chloroquine inhibits
CYP2d6
Chloroquine Increases risk of ventricular arrhythmia when
co-administered with
amiodarone and
halichondrin
T or F
Chloroquine should not be given with mefloquine because of increased risk of seizures
T
T or F
Chloroquine is safe in pregnancy and young children
T
associates with intraerythrocytic hemozoin,
suggesting similarities to the mode of action of
chloroquine
Mefloquine
mefloquine resistance
Increased PFRMD1
Effective therapy for chloroquine-resistant
strains of falciparum
Mefloquine
CYP3A4
mefloquine half life
20 days
AE mefloquine
§ Neurological and psychiatric adverse effects § Epigastric pain § Diarrhea § Abdominal pain § Headache § Rash § Alter cardiac conduction § Leukocytosis, thrombocytopenia, aminotransferases elevation have also been reported
T or F
Pregnancy should be avoided for 3 months after
mefloquine use because of the prolonged half-life
T
T or F
treatment with or after halofranine or
within 2 months of prior mefloquine administration is
contraindicated
T
Considered safe in young children and it is the only
chemoprophylactic agent other than chloroquine
approved for children weighing less than 5 kg
Mefloquine
1ST line therapies for severe falciparum, but its
indication for P. falciparum is no longer used due to
its adverse effects newer drugs are now used
Quinine and quinidine
dextrorotatory stereoisomer of quinine
Quinidine
“General parasitic poison”
Quinine
T or F
Quinine is effective against all four species of
Plasmodium (blood schizonticide)
T
It does decrease DNA strand separation and
transcription, thereby inhibiting protozoal protein
synthesis.
Quinine
AE of quinine/quinidine
Cinchonism
Hypoglycemia
Blackwater fever
T or F
Quinine causes mild uterine contractions when given in 3rd trimester of pregnancy
T
T or F
Quinine should not be given concurrently with mefloquine
T
Primaquine and tafenoquine are classified under ______
tissue schintocides
§ Drug of choice for eradication of dormant liver forms of P. vivax and P. ovale
§ For chemoprophylaxis against all malarial species.
PRIMAQUINE AND TAFENOQUINE
o Medications for P. jiroveci
§ Trimethoprim Sulfamethoxazole
§ Atovaquone
§ Pentamidine and Primaquine
The drug of choice in P. jirovecii
TMZ
Trimethoprim Sulfamethoxazole
Primaquine More serious adverse effect may include:
o Leukopenia
o Agranulocytosis
o Leukocytosis
o Cardiac arrhythmias
§ In Tafenoquine, reported adverse effect may include:
o Headache
o Diarrhea
o Dizziness
§ Component of Malarone
Atovaquone 250 mg +proguanil 100 mg
Treatment and chemoprophylaxis of
falciparum
Atovaquone
MOA of Atovaquone
o Inhibition of mitochondrial electron transport
system in protozoa
Atovaquone half life
2-3 days
Resistance to pyrimethamine:
mutations is
dihydrofolate reductase that decrease the binding
affinity of pyrimethamine
AE DIAMINOPYRIDINES SULFADOXINEPYRIMETHAMINE
§ Occasional skin rashes and reduced
hematopoiesis
§ Excessive doses can produce a megaloblastic
anemia
§ Erythema multiforme, Steven-Johnson’s syndrome,
or toxic epidermal necrolysis
fansidar is a combination of _____ and _____
sulfadoxine and
pyrimethamine
Treatment of Chloroquine Resistant Falciparum
malaria
sulfadoxine and
pyrimethamine
inhibiting protein
synthesis in a plasmodial prokaryote-like organelle,
the apicoplast.
Tetracycline/Doxycycline, clindamycin, Azithromycin
For drugs other than primaquine,
begin 1-2 weeks
before departure (except 2 days before for
Doxycycline and Malarone) and continue for 4
weeks after leaving the endemic area (except 1
week for Malarone).
For P falciparum, P knowlesi, and other
species not identified
admit the patient and
monitor for disease progression
For P falciparum acquired in area with no chloroquine resistance
chloroquine or
hydroxychloroquine (DOC)
For P falciparum acquired in areas with chloroquine resistance
Artemether-lumefantrine (preferred) or Atovaquone-proguanil or Quinine +
tetracycline/doxycycline/clindamycin or Mefloquine
For P falciparum acquired in areas with mefloquine resistance
Artemether-lumefantrine (preferred) or Atovaquone-proguanil or Quinine + tetracycline/doxycycline/clindamycin
DOC is Chloroquine or
hydroxychloroquine
P. malaria
P vivax and P ovale acquired without
chloroquine resistance
chloroquine or
hydroxychloroquine (DOC)
o P vivax acquired in areas with chloroquine
resistance
Artemether-lumefantrine or
Atovaquone-proguanil or Quinine +
tetracycline/doxycycline/clindamycin or
Mefloquine.
To treat dormant liver form you
can add ______
primaquine/tafenoquine
Pregnant women diagnosed with uncomplicated
malaria caused by chloroquine-resistant P.
falciparum infection in the 2nd and 3rd trimesters can
be treated with
artemether-lumefantrine.
In addition, pregnant women of all gestational ages
can be treated with
mefloquine or a combination of
quinine sulfate and clindamycin
T or F
Quinine treatment should continue for 7 days for P.
falciparum infections acquired in Southeast Asia and
for 3 days for infections acquired elsewhere
T
DOC for amebiasis
Metronidazole
characteristic stool of patient with amebiasis
bloody mucoid stool
o Luminal amebicides
§ Diloxanide
§ Paromomycin
§ Iodoquinol
o Systemic amebicides
§ Chloroquine
§ Dehydroemetine
o Mixed amebicides (luminal and systemic)
§ Metronidazole
§ Tinidazole
