Anti-malarials Flashcards
P. falciparum malaria has acquired resistance to ________
chloroquine
Inhibitors of Heme Metabolism: Quinolines
- chloroquine
- quinine
- quinidine
- mefloquine
Inhibitors of Heme Metabolism: Artemisinin Derivatives
- artemisinin
- artesunate
- artemether
- sihydroartemisinin
Inhibitors of Electron Transport
- primaquine
- atovaquone
Inhibitors of Translocation
- doxycycline
- tetracycline
- clindamycin
Inhibitors of Folate Metabolism
- sulfadoxine-pyrimethamine
- proguanil
Which drugs work on the liver stages of malaria?
- atovaquone/proguanil
- primaquine
Quinolines: Names (4)
chloroquine, quinine, quinidine, mefloquine
Quinolines: MOA
inhibits polymerization of Ferriprotoporphyrin IX (heme) to Hemozoin(polymerized heme)–> accumulation of unpolymerized heme leads to oxidative membrane damage that is toxic
Quinolines: Which are taken once a week? (2)
chloroquine and mefloquine
Quinolines: Which are taken every 8 hours? (2)
quinine and quinidine
Quinolines: ADRs: Common (4)
- tinnitus
- headaches
- nausea
- vomiting
Quinolines: ADRs: Serious (3)
- prolonged QT interval
- mefloquine neuropsychiatric effects
- chloroquine toxic at high doses in kids
Quinolines: Chloroquine is a first-line treatment and prophylactic for? (5)
- vivax
- ovale
- malariae
- knowlesi
- senstive strains of falciparum
Quinolines: where is an alternative place to find quinine?
tonic water and can be used prophylactically
Artemisinins: Names
- artemisinin
- artesunate
- artemether
- dihydroartemisinin
Artemisinins: MOA
- forms free radical after activation by iron
- adducts that are toxic to plasmodia
Artemisinins: Pharmacokinetics
co-administration w/ ketoconazole decreases metabolism of artemisinins b/c it is a potent CYP3A4 inhibitor
Artemisinins: ADRs (5)
- nausea
- vomiting
- dizziness
- tinnitus
- type 1 hypersensitivity
Artemisinins: First-line treatment for?
P. falciparum
Artemisinins: USE IN COMBINATION
USE IN COMBINATION
Inhibitors of Electron Transport: Names (2)
primaquine and atovaquone
Inhibitors of Electron Transport: MOA
selectively interrupts the plasmodial ETC
- P = ubiquinone
- A = cytochrome bc1 complex
Inhibitors of Electron Transport: Pharmacokinetics
- metabolized to quinone–> acitve metabolite
- BAD for G6PD pts
- daily dosing for both
Inhibitors of Electron Transport: ADRs (4)
- abdominal pain
- nausea
- hemolytic anemia
- leukopenia
Inhibitors of Electron Transport: Considerations: Primaquine
inhibits hepatic stage caused by vivax and ovale–> DO NOT USE AS MONOTHERAPY==> coadminister w/ doxycycline or proguanil
Inhibitors of Translation: Names (3)
- doxycycline
- tetracycline
- clindamycin
Inhibitors of Translation: MOA
D and T = bind to 30S subunit and blocks binding of tRNA to the A site of mRNA
C = binds to 50S subunit and prevents the transfer of amino acids to the A site
Inhibitors of Translation: Pharmacokinetics
D and T = daily dosing
Inhibitors of Translation: Pregnancy Category for Tetracyclines
D
Inhibitors of Translation: Tetracyclines: ADRs (3)
- photosensitivity
- tooth discoloration and bone development in children
- clostridium difficile diarrhea
Inhibitors of Translation: Clindamycin: ADR
diarrhea caused by Clostridium difficile
Inhibitors of Translation: Used in Combo w/
artesunate or quinine
Inhibitors of Folate Metabolism: Names (2)
- sulfadoxine-pyrimethamine
- proguanil
Inhibitors of Folate Metabolism: MOA
target dihydrofolate reductase(DHFR) and dihydropteroate synthase(DHPS) from the folate metabolic pathway
- S = DHPS
- P = DHFR
Inhibitors of Folate Metabolism: Pharmacokinetics
- S = single dose to treat, weekly/biweekly prophylactic
- P = once daily
Inhibitors of Folate Metabolism: Sulfadoxine-pyrimethamine: ADRs
- discontinue at appearance of rash
- Stevens-Johnson Syndrome or toxic epidermal necrosis
- pruritis, diarrhea, nausea, vomiting, headache
Inhibitors of Folate Metabolism: Proguanil: ADRs
- abdominal pain
- diarrhea
- nausea
- vomiting
- pruritis
- hepatitis
Inhibitors of Folate Metabolism: Sulfadoxine-pyrimethamine: Consideration
highly effective against blood schizont stages of P. falciparum
Inhibitors of Folate Metabolism: Atovaquone-proguanil: Consideration
-blood schizonticides - effective against drug-resistant strains of P. falciparum and P. vivax
E. histolytica lacks ________.
fermentation enzymes - lactate dehydrogenase and pyruvate decarboxylase
E. histolytica is obtained by
ingesting contaminated food/water
Anaerobic organisms contain ___________ which metabolizes pyruvate to acetyl CoA
PFOR = pyruvate-ferredoxin oxidoreductase
Antibiotic: Metronidazole and Tinidazole: MOA
single-electron transfer forms a highly reactive nitro radical anion that kills susceptible organisms by radical-mediated mechanisms that target DNA
Antibiotic: Metronidazole and Tinidazole: Pharmacokinetics
M = dosed every 8 hrs T = dosed daily
Antibiotic: Metronidazole and Tinidazole: ADRs (4)
nausea, headaches, Candida vaginitis, hypersensitivity reaction
Antibiotic: Metronidazole and Tinidazole: Cosiderations
- useful against giardia
- M treats ameba infections
- H. pylori is resistant to M
- T has a shorter treatment course
Antiprotozoal: Nitazoxanide: MOA
- activity against Giardia lamblia and Cryptosporidium parvum
- inhibits PFOR
Antiprotozoal: Nitazoxanide: ADRs (3)
- abdominal pain
- nausea
- headache
Early Stage: African Sleeping Sickness Treatment: Pentamidine
MOA: inhibition of DNA, RNA, and protein synthesis
ADR: fatigue, dizziness, hypotension, pancreatitis, kidney damage
Early Stage: African Sleeping Sickness Treatment: Suramin
MOA: inhibit energy metabolism and RNA polymerase
ADR: pruritis, parethesia, vomiting, nausea
Late Stage: African Sleeping Sickness Treatment: Melarsoprol
MOA: inhibits trypanosomal pyruvate kinase–> inhibits glycolysis and decreases ATP production
ADR: toxic to humans, phlebitis, brian inflammation
Late Stage: African Sleeping Sickness Treatment: Eflornthine
-early and late stage West NOT East
MOA: irrerversible inhibitor of ornithine decarboxylase and inhibits polyamine synthesis–> inhibits nucleic acid and protein synthesis
ADR: less toxic that melasoprol, acne
Chaga’s Treatment: Nifurtimox
MOA: toxic oxygen free radicals inside parasite
ADR: anorexia, vomiting, memory loss, sleep disorders, seizures
Leishmania Treatments: Sodium stibogluconate and Meglumin antimonate
MOA: pentavalent antimony and inhibition of glycolytic pathway and fatty acid oxidation
ADR: prolonged QT interval, pancreatitis, rash
Leishmania Treatments: Alternative
amphotericin and miltefosine
Anthelmintic: Ivermectin: MOA
activation of glutamate-gated chloride channels causes a blockade of neuromuscular transmission and paralysis of the worm
Anthelmintic: Ivermectin: Pharmacokinetics
single dose
Anthelmintic: Ivermectin: ADRs (2)
- inflammatory or allergic response
- seizures
Anthelmintic: Albendazole, Mebendazol, Triclabendazole: MOA
inhibits tubulin polymerization —> disrupts nematodal motility and DNA replication–> immobilization and death
Anthelmintic: Albendazole, Mebendazol, Triclabendazole: Pharmacokinetics
A = dosed daily
M and T = every 12 hours
Anthelmintic: Albendazole, Mebendazol, Triclabendazole: ADRs (5)
- vomiting
- nausea
- diarrhea
- increased liver enzymes
- Stevens-Johnson Syndrome
Anthelmintic: Albendazole, Mebendazol, Triclabendazole: Consideration
used effective contraception during treatment and 3 days after final dose
Antifilarial Agent: Diethylcarbamazine: MOA
unknown
Antifilarial Agent: Diethylcarbamazine: Pharmacokinetics
dosed daily
Antifilarial Agent: Diethylcarbamazine: Pregnancy Category
X
Antifilarial Agent: Diethylcarbamazine: Indication
adult filariasis worms
Antifilarial Agent: Diethylcarbamazine: ADRs (3)
anorexia, headache, nausea
Anthelmintic: Praziquantel: MOA
contraction and paralysis of worm
Anthelmintic: Praziquantel: Pharmacokinetics
dosed every 8 hrs
Anthelmintic: Praziquantel: Indications
adult cestode(tapeworm) and trematode(fluke) infections
Anthelmintic: Praziquantel: ADRs (3)
nausea, headache, and abdominal discomfort
