Term
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Definition
antimalarial agent
MOA: a rxn catalyzed by heme iron -> carbon-centered radical -> alkylates and damages parasite's macromolecules
USE: treat severe P falciparum infections, key role in combination therapy for drug-resistant infections
-CURRENTLY NOT FDA APPROVED
-not used alone because of incomplete efficacy and avoid drug resistance
-not used prophylactically |
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Term
| Sulfonamides (Sulfoxadine) |
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Definition
antimalarial agent
MOA: inhibit dihydropteroate synthase -> inhibit folate synthesis
USE: use in combo with chloroquine in tx and prevention of malaria |
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Term
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Definition
antimalarial agent
MOA: inhibits plasmodial dihydrofolate reductase -> inhibit folate synthesis
USE: used in combo with chloroquine for tx and prevention of malaria |
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Term
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Definition
antimalarial agent
MOA: unknown
USE: DOC-eradication of dormant P vivax and ovale liver forms-RADICAL CURE FOR THESE MALARIAL SPECIES, gametocidal against the 4 malaria species; active against hepatic stages but very weak against erythrocytic stage
PK: well absorbed from GI, long half life -> weekly dosing prophylaxis
-never give parenterally -> induce hypotension
SE: generally well tolerated, may produce GI symptoms
TOX: blood dyscrasias, cardiac arrythmias; hemolysis or methomyoglobinemia (cyanosis) in persons with G6PD deficiency
CI: pts receiving myelosuppressive drugs or history of granulocytopenia
-avoid in pregnancy because of effects on fetus
STANDARD THERAPY: chloroquine to eradicate erythrocytic forms, if G6PD levels normal, then 14 day primaquine course to eradicate liver parasites and prevent relapse |
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Term
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Definition
antimalarial agent
MOA: strong blood schizonticidal activity against P falciparum and P vivax, not active against hepatic stages or gametocytes
USE: prophylactic agent in most malarial regions with chloroquine-resistant strains (weekly dosing)
PK: oral, well absorbed, widely distributed, elimated slowly allowing single-dose treatment regime
MOR: sporadic resistance-associated with quinine but not chloroquine
SE: CNS, blood dyscrasias, heart, GI
-FDA approved only for malaria prophylaxis |
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Term
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Definition
antimalarial agent
MOA: tx of choice/standard therapy in US for severe F malaria; gametocidal against P vivax and P ovale but not P falciparum
USE: 1st line therapy for F malaria; quinine-highly effective blood schizonticide against 4 forms of human malaria parasites; not used prophylactically
PK: oral quinine rapidly absorbed, or IV or IM, widely distributed
TOX: cardiac toxicity and unpredictable PKs (cardiac monitoring); discontinue if severe cinchonism, hypersensitivtiy, hemolysis occur
SE: cinchonism (tinnitus, headache, nausea, dizziness, flushing, visual disturbances); prolonged use -> GI disturbances, hypersensitivity (blackwater fever-hemolysis, hemoglobinuria), hematological abnormalities, hypoglycemia, uterine contractions
DI: do not give with mefloquine
-given with doxycycline to limit duration of use (3 days) due to toxicity
-not active against liver parasites |
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Term
Helminthic diseases
Nematodes:
Cestodes:
Trematodes: |
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Definition
Nematodes: Pyrantel pamoate, Piperazine, Mebendazole
Cestodes: Praziquantel, Niclosamide
Trematodes: Praziquantel |
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Term
Protozoan Infections
Trypanosomiasis
African:
American:
Leismaniasis:
Ambiasis:
Giardiasis:
Thrichomoniasis:
Balantidiasis: |
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Definition
Trypanosomiasis
African: Suramin, Melarsoprol, Eflornithine
American: Nifurtimox
Leismaniasis: Sodium stibogluconate
Ambiasis: Metronidazole, Iodoquinol, Paramonycin
Giardiasis: Metronidazole, Nitazoxanide
Thrichomoniasis: Metronidazole
Balantidiasis: Tetracycline |
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Term
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Definition
Nematodes
USE: DOC-hydatid disease; combo w/ CSs for neurocysticercosis; also ascariasis, pinworm, hookworm infections
PK: admin PO to fasting pts with intraluminal parasites or with fatty meal when treating tissue infections
SE: generally well tolerated (1-3 days drug regime), long-term use -> enzymatic liver alterations and blood disorders
-careful use in pregnancy |
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Term
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Definition
Cestodes
salicylamide derivative
MOA: inhibition of oxidative phosphorylation
USE: treatment of most cestode infections
PK: oral admin
SE: mild or transient common GI rxns
-avoid alcohol |
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Term
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Definition
Cestodes and Trematodes
synthetic isoquinoline-pyrazine derivative
MOA: increases parasite cell membrane permeability to Ca2+ -> produce paralysis, dislodgement, death
USE: cestode and trematode infections, effective tx of schistosome infections of all specifies
PK: well absorbed from GI
SE: well tolerated and safe, nausea, dizziness, abdominal discomfort -> incidence and severity of SEs increases with dose
CI: pregnancy |
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Term
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Definition
Nematodes
MOA: inhibit microtubule synthesis
USE: ascariasis, pinworm, hookworm infections
PK: oral absorption increased if injested with fatty meal
SE: short term well tolerated
CI: pregnancy |
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Term
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Definition
Nematodes
MOA: inhibit ACh at myoneural junction -> produce nematode flaccid paralysis -> expulsion
USE: alternative to mebendazole for treatment of ascariasis
PK: rapidly absorbed
SE: may cause dizziness, urticaria
CI: known hypersensitivity, epilepsy, renal or hepatic disorders |
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Term
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Definition
Nematodes
ganglionic nicotinic ACh agonist
MOA: produce muscular contraction of nematode
USE: luminal ascariasis, pinworm, hookworm infections
PK: poorly absorbed
SE: well tolerated, generally only need single dose -> parasite paralysis and expulsion |
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Term
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Definition
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Term
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Definition
Giardiasis
MOA: blocks pyruvate:ferredoxin oxidoreductase pathway
USE: effective against G lamblia and metronizadole resistant protozoa strains and several tapeworm helminths |
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Term
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Definition
Amebiasis
USE: luminal amebecide
-little GI absorption, may accumulate in renal insufficiency and cause renal toxicity
SE: generally well tolerate, GI issues |
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Term
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Definition
Amebiasis
-derivative of Emetine
USE: effective against E histolytica trophozoites in bowel lumen but not in intestinal wall or extraintestinal tissues, combo w/ metronidazole
SE: generally well tolerated
-caution in pts with optic neuropathy, renal, thyroid disease, or iodine intolerance |
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Term
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Definition
Amebiasis, Giardaisis, Thrichomoniasis
Abebiasis: DOC, effectively eliminates intestinal and extraintestinal E histolytica infections
MOA: penetrates protozoan and bacterial cells, does not enter mammalian cells; affects the ferredoxin-like or flavodoxin-like low redox-potential electron transport proteins -> FUNCTIONS AS ELECTRON SINK -> toxic intermediates
PK: well absorbed after oral admin, widely distributed with intracellular conc. approaching extracelular levels, metabolized in liver
SE: nausea, vomiting, cramps, turns urine dark or red brown
CI: pregnancy or nursing, DO NOT DRINK ALCOHOL |
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Term
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Definition
Leismaniasis
antimonial
USE: choice drug for all forms, cutaneous and visceral, efficacy depends on many factors
PK: daily doses given IM or IV for 3-4 weeks (cure)
SE: intially relatively well tolerated but can produce dose related toxicity -> fever, GI changes, ECG changes (T-wave inversions/prolonged QT intervals) |
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Term
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Definition
American Trypanosomiasis
USE: tx of acute, but not chronic form of disease
-in many cases does not eradicate parasite and get chronic form
SE: severe GI, CNS, neurological toxicity |
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Term
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Definition
African Trypanosomiasis
MOA: inhibits enzyme ornithine decarboxylase -> blocks conversion of ornithin to putrescine which is required for cell proliferation
USE: tx of CNS advanced disease
TOX: better tolerated than arsenicals but still see significant blood and GI toxicity-reversible |
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Term
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Definition
African Trypanosomiasis
arsenical
USE: 1st line therapy for advanced CNS infections
PK: IV, penetrates CNS
TOX: use only when absolutely necessary-serious GI, CV, renal, hepatic SEs, encephalopathy (fatal), hemolysis in GP6D deficient pts |
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Term
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Definition
African Trypanosomiasis
USE: chemoprophylaxis and tx of early hemolymphatic infections, combo w/ pentamidine may increase efficacy
PK: IV, does not cross BBB -> not effective against advanced forms of disease
SE: serious GI, CV, neurological, blood |
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Term
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Definition
antimalarial agent
-few areas infested only by this drug-sensitive malaria parasites (Caribbean, Central America, Middle East)
MOA: interfere with heme handling -> failure to inactivate heme results in oxid. damage and causes parasite death
USE: DOC-treatment of nonfalciparum and sensitive falciparum malaria-rapidly terminates fever and clears parasitemia; preferred chemoprophylactic in regions without resistant F malaria
PK: well absorbed from GI, IM or IV not good, rapidly distributed, complex PKs
MOR: mutations in gene encoding chloraquine resistance transporter (crt); resistance common among P falciparum but not so common for P vivax
TOX: usually well tolerated, even with prolonged use; pruitis, anorexia, vision blurring; rare rxns-hemolysis in G6PD deficiency, confusion, ECG changes
CI: pts with psoriasis or porphyria
-highly effective blood schizonticide, principle antimalarial drug in world
-not active against liver parasites
-does not eliminate dormant liver forms of P vivax or P ovale
-safe in pregnancy and for small children |
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