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29 Cards in this Set
- Front
- Back
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Be able to list the categories (and sub-categories) of antiprotozal drugs and the drugs given in each category (subcategory).
Explain each drug MA and site of action, pharmacokinetics and adverse effects. Understand the rationale for a drug being used in a particular situation. Be able to describe the life cycle of Entamoeba histolytica. Be able to describe the life cycle of the malarial parasites. Be able to differentiate amebiasis, malaria, trypanosomiasis, leishmaniasis, toxoplasmosis and giardiasis and any relevant subcategories of each. Understand the concept of resistance and how this might effect a treatment for a condition. |
Objectives
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How is amebic dysentery caused by entamoeba histolytica diagnosed?
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isolating E. histolytica from fresh feces.
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entamoeba histolytica cysts are ingested --> ____________ form in ileum --> replicate in bowel walls --> can cause systemic infection (liver) --> _____ reform in rectum
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entamoeba histolytica cysts are ingested --> trophozoites form in ileum --> replicate in bowel walls --> can cause systemic infection (liver) --> cysts reform in rectum
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Classification of amebicidal drugs
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Classification of amebicidal drugs
Luminal, Systemic, Mixed (luminal and systemic) luminal conc is too low to use "mixed" alone for lumen) |
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Metronidazole (FLAGYL)
_____ amebicide of choice for treating amebic infections. Kills the E. histolytica trophozoites (not _____) Broad spectrum of activity against protozoa and anaerobic bacteria. Metronidazole activated when reduced by ferre______ or their equivalents in protozoa or bacteria. The nitro group of metronidazole is able to serve as an electron ________, forming reduced cytotoxic compounds that bind to proteins and DNA leading to inhibition of protein synthesis and DNA strand breakage, resulting in cell death. |
Metronidazole (FLAGYL)
Mixed amebicide of choice for treating amebic infections. Kills the E. histolytica trophozoites (not cysts) Broad spectrum of activity against protozoa and anaerobic bacteria. Metronidazole activated when reduced by ferredoxins or their equivalents in protozoa or bacteria. The nitro group of metronidazole is able to serve as an electron acceptor, forming reduced cytotoxic compounds that bind to proteins and DNA leading to inhibition of protein synthesis and DNA strand breakage, resulting in cell death. |
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Metronidazole
NOTE: for the treatment of amebiasis usu. admin. with a luminal amebicide, such as dil_______ f______, i_________, or paramo_____.(comb. provides cure rates > 90%.) |
Metronidazole
NOTE: for the treatment of amebiasis usu. admin. with a luminal amebicide, such as diloxanide furoate, iodoquinol, or paramomycin.(comb. provides cure rates > 90%.) |
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Metronidazole
DOC mild-severe amebiasis, g_________, t_____________; also bacterial vaginosis |
Metronidazole
DOC mild-severe amebiasis, giardiasis, trichomoniasis; also bacterial vaginosis |
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Metronidazole
Adverse effects: Most common assoc. with GI tract (N, V, epigastric distress, and abdominal cramps) Unpleasant ________ taste often experienced. Other effects: Oral moniliasis (_____ infection of the mouth) and rarely neurotoxic problems (dizziness, vertigo, & numbness or paresthesias in the peripheral nervous system. If taken with alcohol a di________-like effect. Contraind in 1st/Trim. pregnancy (mutagenic/carcinogenic/rats) and nursing women DOC Clostridium difficile (pseudomem. colitis) New: tinidazole (TINDAMAX) TID 5 days CYP450 inhibitor (potentiates warfarin metabolism) |
Metronidazole
Adverse effects: Most common assoc. with GI tract (N, V, epigastric distress, and abdominal cramps) Unpleasant metallic taste often experienced. Other effects: Oral moniliasis (yeast infection of the mouth) and rarely neurotoxic problems (dizziness, vertigo, & numbness or paresthesias in the peripheral nervous system. If taken with alcohol a disulfiram-like effect. Contraind in 1st/Trim. pregnancy (mutagenic/carcinogenic/rats) and nursing women DOC Clostridium difficile (pseudomem. colitis) New: tinidazole (TINDAMAX) TID 5 days CYP450 inhibitor (potentiates warfarin metabolism) |
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how do you know if person on metronidazole has alcohol?
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flushing, nausea, vomiting, SOB, tachycardia (hangover)
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Does metronidazole cross the BBB?
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yes
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Iodoquinol (YODOXIN)
_______ amebicide, iodine compound, only 10% systemically absorbed MA _______ ; 650 mg tid x 20d Effects on cysts & trophozoites in GI, main use in asymptomatic cyst carriers and follow-up to metronidazole GI disturbances, rash; high doses may cause enlarged _______, some neurotoxicity (neuropathy/visual disturbances) Risk of optic neuritis, atrophy, possible loss of vision (rare, large doses over time) |
Iodoquinol (YODOXIN)
Luminal amebicide, iodine compound, only 10% systemically absorbed MA unknown ; 650 mg tid x 20d Effects on cysts & trophozoites in GI, main use in asymptomatic cyst carriers and follow-up to metronidazole GI disturbances, rash; high doses may cause enlarged thyroid, some neurotoxicity (neuropathy/visual disturbances) Risk of optic neuritis, atrophy, possible loss of vision (rare, large doses over time) |
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Paromomycin (HUMATIN)
____(type)____ antibiotic; 25 mg/kg 3X per day x 7 days Little PO absorption, _______ amebicide Direct amebicidal effect (Inhibits protein synthesis leading to an effect on cell membranes – causing leakage) Used in amebiasis, t________, g_________, c________________ (HIV) with limited effect GI disturbances N-V-D, abd. pain; superinfection |
Paromomycin (HUMATIN)
Aminoglycoside antibiotic; 25 mg/kg 3X per day x 7 days Little PO absorption, luminal amebicide Direct amebicidal effect (Inhibits protein synthesis leading to an effect on cell membranes – causing leakage) Used in amebiasis, tapeworms, giardiasis, cryptosporidiosis (HIV) with limited effect GI disturbances N-V-D, abd. pain; superinfection |
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Diloxanide Furoate (FURAMIDE)
_______ amebicide, 500 mg tid x 10d MA _______, converted to active free ____ form in the gut Usu used to treat asymptomatic ____ carriers and follow-up to metronidazole Excessive __________, N-V-D, pruritis; dizziness/double vision less common Not used much in US |
Diloxanide Furoate (FURAMIDE)
Luminal amebicide, 500 mg tid x 10d MA unknown, converted to active free base form in the gut Usu used to treat asymptomatic cyst carriers and follow-up to metronidazole Excessive flatulence, N-V-D, pruritis; dizziness/double vision less common Not used much in US |
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Systemic Amebicides
These drugs useful for treating liver absesses or intestinal wall infections caused by amebas. C__________ E______ |
Systemic Amebicides
These drugs useful for treating liver absesses or intestinal wall infections caused by amebas. Chloroquine Emetine |
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Chloroquine
Used in combination with _____________ and diloxanide furoate to treat and prevent amebic liver a________. Eliminates trophozoites in liver abscesses (not useful in treating _______ amebiasis) Also effective in treatment of M______ |
Chloroquine
Used in combination with metronidazole and diloxanide furoate to treat and prevent amebic liver abscesses. Eliminates trophozoites in liver abscesses (not useful in treating luminal amebiasis) Also effective in treatment of Malaria |
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Emetine (not given IV)
Emetine and dehydroemetine (______ alkaloids) are alternative agents for the treatment of amebiasis. They inhibit protein synthesis by blocking chain elongation. __ injection preferred route. Use limited by toxicities (dehydroemetine less toxic than emetine). Close clinical observation necessary. Not to take > 10 days. Ipecac make you __ |
Emetine (not given IV)
Emetine and dehydroemetine (ipecac alkaloids) are alternative agents for the treatment of amebiasis. They inhibit protein synthesis by blocking chain elongation. IM injection preferred route. Use limited by toxicities (dehydroemetine less toxic than emetine). Close clinical observation necessary. Not to take > 10 days. Ipecac make you yac |
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Emetine
Adverse effects: pain at injection site, transient nausea, ______toxicity (arrhythmias or congestive heart failure), neuromuscular weakness, dizziness, and rashes this is only used as a "back-up" for pts in the ________ |
Emetine
Adverse effects: pain at injection site, transient nausea, cardiotoxicity (arrhythmias or congestive heart failure), neuromuscular weakness, dizziness, and rashes this is only used as a "back-up" for pts in the hospital |
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Malaria
Acute infectious disease caused by 4 species of the protozoal genus P_________. Parasite transmitted to humans by the bite of a female _________ mosquito (thrives in humid swampy areas) Plasmodium f_________ Plasmodium v____ Plasmodium m_______ Plasmodium o_____ |
Malaria
Acute infectious disease caused by 4 species of the protozoal genus Plasmodium. Parasite transmitted to humans by the bite of a female anopheles mosquito (thrives in humid swampy areas) Plasmodium falciparum Plasmodium vivax Plasmodium malariae Plasmodium ovale |
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Plasmodium falciparum
Most _________ species Causes an acute, rapidly fulminating disease that is characterized by persistent high fever, orthostatic ____tension, and massive erythro_______ (an abnormal elevation in the number of red blood cells accompanied by swollen and reddish condition of the limbs). Can lead to capillary obstruction and death if treatment is not instituted promptly. |
Most dangerous species
Causes an acute, rapidly fulminating disease that is characterized by persistent high fever, orthostatic hypotension, and massive erythrocytosis (an abnormal elevation in the number of red blood cells accompanied by swollen and reddish condition of the limbs). Can lead to capillary obstruction and death if treatment is not instituted promptly. |
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Plasmodium vivax
Causes a ______ form of the disease. |
Causes a milder form of the disease.
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Plasmodium malariae
Common to many ________ regions. |
Plasmodium malariae
Common to many tropical regions. |
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Plasmodium ovale
______ encountered |
Plasmodium ovale
Rarely encountered |
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Malaria
insect injects sporo______ --> become ____zoites in the liver --> RBCs invaded --> ______zoites form and replicate in RBC --> RBC explodes releasing ____zoites --> ______cytes form and insects pick them up |
Malaria
insect injects sporozoites --> become merozoites in the liver --> RBCs invaded --> trophozoites form and replicate in RBC --> RBC explodes releasing merozoites --> gametocytes form and insects pick them up |
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Important Note:
Resistance acquired by the mosquito to insecticides, and by the parasite to drugs, has led to new therapeutic challenges (particularly in the treatment of P. __________). |
Resistance acquired by the mosquito to insecticides, and by the parasite to drugs, has led to new therapeutic challenges (particularly in the treatment of P. falciparum).
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Malaria Parasite Life Cycle Stages
Pre-____________ stage- bite injects sporocytes in blood and goes to liver (1st hr.) __________cytic stage – in liver 10-14 days, forms ____zoites: 2nary tissue forms remain in liver/become dormant (P. vivax/ovale) Erythrocytic stage – RBC: releases ____zoites every 3 or 4 days with fever ______cyte stage – sexual forms ingested by biting female mosquito |
Malaria Parasite Life Cycle Stages
Pre-erythrocytic stage- bite injects sporocytes in blood and goes to liver (1st hr.) Exoerythrocytic stage – in liver 10-14 days, forms merozoites: 2nary tissue forms remain in liver/become dormant (P. vivax/ovale) Erythrocytic stage – RBC: releases merozoites every 3 or 4 days with fever Gametocyte stage – sexual forms ingested by biting female mosquito |
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Malaria Parasite Life Cycle Info.
Only _______cytic parasites cause clinical illness. In P. falciparum and P. malariae infection, only one cycle of liver cell invasion and multiplication occurs, and liver infection ceases spontaneously in less than _ weeks. Thus treatment that eliminates ____________ parasites will cure these infections. In P. vivax and P. ovale infections, a dormant hepatic stage, the _____zoite, is not eradicated by most drugs, and subsequent relapses can therefore occur after therapy directed against erythrocytic parasites. Eradication of both erythrocytic and _______ parasites is required to cure these infections. |
Malaria Parasite Life Cycle Info.
Only erythrocytic parasites cause clinical illness. In P. falciparum and P. malariae infection, only one cycle of liver cell invasion and multiplication occurs, and liver infection ceases spontaneously in less than 4 weeks. Thus treatment that eliminates erythrocytic parasites will cure these infections. In P. vivax and P. ovale infections, a dormant hepatic stage, the hypnozoite, is not eradicated by most drugs, and subsequent relapses can therefore occur after therapy directed against erythrocytic parasites. Eradication of both erythrocytic and hepatic parasites is required to cure these infections. |
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Note
Diagnosis of Malaria depends on laboratory ID of the parasites in ____ ____ _____ of peripheral blood smears. |
Note
Diagnosis of Malaria depends on laboratory ID of the parasites in red blood cells of peripheral blood smears. |
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Classes of Antimalarial Drugs
Tissue ________icides: eliminate developing or dormant liver forms _____ Schizonticides: act on erythrocytic parasites ______cides: kill sexual stages and prevent transmission to mosquitoes No available agent can reliably effect a radical cure (elim both hepatic and erythrocytic stages). All effective chemoprophylactic agents kill erythrocytic parasites before they grow sufficiently in number to cause clinical disease |
Tissue Schizonticides: eliminate developing or dormant liver forms
Blood Schizonticides: act on erythrocytic parasites Gametocides: kill sexual stages and prevent transmission to mosquitoes No available agent can reliably effect a radical cure (elim both hepatic and erythrocytic stages). All effective chemoprophylactic agents kill erythrocytic parasites before they grow sufficiently in number to cause clinical disease |
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Strategies for Prevention and Treatment
Kill the mosquitoes Don’t get stung by the mosquitoes Prophylaxis – blood schizonticides (ery. cycle) used for suppressive prophylaxis, prevent symptoms of disease, not infection Clinical cure – blood _______ticides (ery. cycle) used to kill all erthrocytic forms _______ cure – elimination of all erythrocytic and secondary tissue forms With P. falciparum/P. malariae clinical cure is a _______ cure |
Strategies for Prevention and Treatment
Kill the mosquitoes Don’t get stung by the mosquitoes Prophylaxis – blood schizonticides (ery. cycle) used for suppressive prophylaxis, prevent symptoms of disease, not infection Clinical cure – blood schizonticides (ery. cycle) used to kill all erthrocytic forms Radical cure – elimination of all erythrocytic and secondary tissue forms With P. falciparum/P. malariae clinical cure is a radical cure |
