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79 Cards in this Set
- Front
- Back
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what initiates human infection with malaria
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anopheline mosquito inoculates sporozoites
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circulating sporozoites infect
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rapidly invade liver cells-schizonts mature here
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what are released from liver in malaria infection
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merozoites-they invade RBCs
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which species of malaria only have one cycle of liver cell invasion
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falciparum and malariae; liver infection ceases spontaneously in less than 4 weeks
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dormant hepatic stage with vivax and ovale malarial infections
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hyponozoite-not eradicated by most drugs and relapses occur; must eradicate RBC and liver parasites to cure
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tissue schizonticides
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drugs that eliminate developing or dormant liver forms
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blood schizonticides
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drugs that act on RBC parasites
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gametocides
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drugs that kill sexual stages and prevent transmission to mosquitos
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causal prophylactic drugs
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capable of preventing erythrocytic infection; most only kill RBC parasites b4 increase sufficiently to cause clinical disease
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prophylaxis for malaria
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chloroquine for non drug resistant areas; mafloquine or Malarone for most areas; doxycycline for high resistant areas (Thailand)
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what drug is most commonly used to eradicate liver forms (ovale and vivax infections)
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primaquine
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what is falciparum malaria treated with in most areas
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oral quinine or IV quinidine plus doxycycline (or clindamycin for kids)
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Chloroquine specs
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rapidly/almost completely absorbed from GI; max concentration 3 hours, rapid distribution to tissues; excreted in urine with half-life 3-5 days, terminal half-life 1-2 months
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Chloroquine MOA
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concentrating in parasite food vacuoles, preventing biocrystallization of hemoglobin breakdown product heme into hemozoin-eliciting parasite toxicity due to buildup of free heme
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chloroquine resistance cause
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mutations in putative transporter PfCRT
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what is chloroquine being replaced by
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artemisinin-based combination therapies
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rare rxns with chloroquine use
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hemolysis in G6PD-deficient ppl; impaired hearing, confusion, psychosis, seizures, agranulocytosis, exfoliative dermatitis, alopecia, bleaching of hair, hypotension, EKG changes
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long term high dose chloroquine for rheumatologic diseases can cause
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irreversible ototoxicity, retinopathy, myopathy, and peripheral neuropathy
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contraindications for chloroquine use
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psoriasis or porphyria
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quinidine
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dextrorotary sterioisomer of quinine
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quinine metabolism
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liver and excreted in urine
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quinine MOA
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unknown; rapid-acting, highly effective blood schizonticide against 4 species of malaria
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quinine and non-falciparum species treatment
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less effective than chloroquine and more toxic
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quinine and Babesia microti
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first-line therapy along with clindamycin
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cinchonism with quinine and quinidine
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tinnitus, headache, nausea, dizziness, flushing, and visual disturbances; occurs at therapeutic dosages
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what is a particular problem of quinine and quinidine in pregnant patients
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hypoglycemia via stimulation of insulin release-pregnant patients have increased sensitivity to insulin; can also stimulate uterine contractions, effect mild
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Blackwater fever
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rare severe illness with marked hemolysis and hemoglobinuria in setting of quinine therapy for malaria; appears to be due to hypersensitivity rxn, pathogenesis uncertain
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contraindications for quinine and quinidine
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discontinue if severe cinchonism, hemolysis, hypersensivity occur; avoid if underlying visual or auditory problems, and cardiac abnormalities
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what can block absorption of quinine/quinidine
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aluminum containing antacids
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mefloquine specs
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chemically related to quinine; only oral administration; well absorbed; terminal elimination 20 days-weekly dosing; slowly excreted in feces
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mefloquine MOA
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unknown; strong blood schizonticidal; not acitve against hepatic stages or gametocytes
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adverse effects of mefloquine
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leukocytosis, thrombocytopenia, and aminotransferase elevations reported; neuropsychiatric symptoms (<1/1000); cardiac conduction-arrhythmias and bradycardia
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contraindications with mefloquine
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history of epilepsy, psychiatric disorders, arrhythmia, cardiac conduction defects, or sesitivity to related drugs
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primaquine specs
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well absorbed in GI, plasma half-life 3-8 hours; rapidly metabolized and excreted in urine
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3 major metabolites of primaquine cause
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less antimalarial activity, but more potential for inducing hemolysis than parent cmpd
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action of primaquine
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dormant hynozoite stagees, erythrocytic stages-weak, and gametocidal in all 4 species
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more serious rare adverse effects of primaquine
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leukopenia, agranulocytosis, leukocytosis, and cardiac arrhythmias; hemolysis or methemoglobinemia in G6PD deficiency ppl
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contraindications of primaquine
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history of granulocytopenia or methemoglobinemia, receiving myelosuppressive drugs (like quindine)
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why is primaquine avoided in pregnancy
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fetus is relatively G6PD deficient and thus at risk for hemolysis
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Atovaquone MOA
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disrupt mitochondrial ETC; active against tissue and RBC schizonts
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chemoprophylaxis lenth of various anti-malarials
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1 week after exposure for atovaquone; 4 weeks for mefloquine or doxycycline (lask activity against schizonts)
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Malarone components and use
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atovaquone (250 mg) and proguanil (100 mg); treatment and chemoprophylaxis of falciparum
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tetracycline or rifampin use with Malarone
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plasma concentrations decreased 50%
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pyrimethamine specs
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inhibits folate synthesis; half-life 3.5 days; extensively metabolized
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proguanil specs
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inhibits folate synthesis; half-life 16 hours; prodrug (cycloguanil acitve metabolite)
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MOA of pyrimethamine and proguanil
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selectively inhibit plasmodial dihydrofolate reductase
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what do sulfonamides and sulfones inhibit
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dihydropteroate synthase
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Fansidar consists of
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sulfadoxine-pyrimethamine
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first line therapy against toxoplasmosis
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pyrimethamine with sulfadiazine
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first line therapy against P jiroveci
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trimethoprim plus sulfamethoxazole
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Fansidar rare, but severe rxns
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cutaneous rxns like erythema multiforme, Steven-Johnson syndrome, and toxic epidermal necrolysis
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tetracycline and doxycycline are active agaisnt what in malaria
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erythocytic schizonsts of all 4 species
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spiramycin use
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macrolide antibiotic used to treat primary Toxoplasmosis acquired during pregnancy
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Halofantrine hydrochloride
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active against erythrocytic stages in all 4 species of malaria; half-life 4 days; fecal excretion
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concerning effects of Halofantrine hydrochloride
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cardiac conduction alteration-seen with standard doses, worsened by mefloquine therapy; embryotoxic
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Lumefantrine
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4.5 hour half-life; CYP3A4 metabolism; no dangerous cardiac effects like Halofantrine hydrochloride
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artemisinin and derivatives
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only oral; half-life 1-3 hrs; rapidly metabolized to acitve dihydroartemisinin
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artemisinin and derivatives activity
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rapidly active blood schizonticides against all 4 species of malaria; no hepatic stage effects
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artemisinin and derivatives possible MOA
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production of free radicals that follows iron-catalyzed cleavage of artemisinin endoperoxide bridge in parasite food vacuole or inhibition of parasite Ca2+ ATPase
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rare serious toxicity of artemisinin and derivatives
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neutropenia, anemia, hemolysis, elevated liver enzymes, allergic rxns
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treatment of asymptomatic entamoeba histolytica carriers
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not treated in endemic areas, with liminal amebicide in nonendemic areas
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standard luminal amebicides
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diloxanide furoate, iodoquinol, and paromomycin
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treatmnt for amebic colitis and dysentery
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metronidazole plus luminal amebicide
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metronidazole and entamoeba histolytica
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kills trophozoites, but not cysts; eradicates intestinal and extraintestinal infections
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tinidazole
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similar activity as metronidazole and better toxicity profile; also has simpler dosing regimens
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metronidazole excretion
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mainly urine, decreased clearance with impaired liver fxn
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metronidazole MOA
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nitro group chemically reduced in anaerobic bacteria and sensitive protozoans
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adverse effects of metronidazole
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common: nausea, headache, dry mouth, metallic taste; infrequent: vomiting, diarrhea, insomnia, weakness, dizziness, thrush, rash, dysuria, dark urine, vertigo, paresthesias, neutropenia; rare: pancreatitis and CNS toxicity; disulfuram-like effect
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iodoquinol
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effective luminal amebicide used commonly with metronidazole; 90% retained in intestine; unknown mechanism
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iodoquinol and iodine
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increases protein-bound serum iodine leading to decrease in measured I-131 uptake that persists for months
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diloxanide furoate
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effective luminal amebicide; split into diloxanide and furoic acid; MOA unknown; drug of choice for asymptomatic luminal infections
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paromomycin sulfate
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aminoglycoside antibiotic not absorbed significantly in GI tract; used only as luminal amebicide
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pentamidine activity
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against trypanosomatid protozoans and P jiroveci; significant toxicity; MOA unknown
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pentamidine adverse effects
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highly toxic-50% have adverse effects; pancreatic toxicity, hypoglycemia, reversible renal insufficiency; rash, metallic taste, fever, Gi symptoms, abnormal LFT, hypocalcemia, thrombocytopenia, hallucinations, cardiac arrhythmias
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sodium stibogluconate specs
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first line for cutaneous and visceral leishmaniasis; MOA unknown
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nitrozoxanide uses and MOA
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giardia lamblua and cryptosporidium parvum; active metabolite tizoxanide inhibits pyruvate:ferredoxin oxidoreductase pathway
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suramin specs
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first line for E african trypanosomiasis; doesn't enter CNS; unknown MOA
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most important toxicity of melarsoprol (used in trypanosomiasis)
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reactive encephalopathy-generally appears within 1st week of therapy; likley due to disruption of trypanosomes in CNS
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eflornithine MOA (trypanosomiasis treatment)
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inhibitor of ornithine decarboxylase; W african first line, not effective for E african disease
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