Podcast
Questions and Answers
Which medication is the only one effective for the elimination of hypnozoites?
Which medication is the only one effective for the elimination of hypnozoites?
- Primaquine (correct)
- Mefaloquine
- Quinine
- Chloroquine
What is the primary mechanism of action of chloroquine against malaria?
What is the primary mechanism of action of chloroquine against malaria?
- Inhibiting RNA synthesis
- Disrupting mitochondrial function
- Forming complexes with heme to prevent crystallization (correct)
- Blocking folate metabolism
In what situation is chloroquine contraindicated?
In what situation is chloroquine contraindicated?
- In patients with psoriasis (correct)
- In patients with fever
- In patients taking NSAIDs
- In healthy adults without malaria
Which statement about chloroquine is true?
Which statement about chloroquine is true?
Which of the following treatments can lead to hypoglycemia as a side effect?
Which of the following treatments can lead to hypoglycemia as a side effect?
What is the preferred chemoprophylactic agent in areas where there is no resistant P falciparum malaria?
What is the preferred chemoprophylactic agent in areas where there is no resistant P falciparum malaria?
Which drug can be used both for treatment and prophylaxis of malaria?
Which drug can be used both for treatment and prophylaxis of malaria?
Which side effect is common across all quinoline derivatives?
Which side effect is common across all quinoline derivatives?
What type of organisms are classified as helminths?
What type of organisms are classified as helminths?
Which species of Plasmodium is not recognized for causing malaria in humans?
Which species of Plasmodium is not recognized for causing malaria in humans?
What is the role of gametocides in malaria treatment?
What is the role of gametocides in malaria treatment?
What do blood schizonticides specifically target?
What do blood schizonticides specifically target?
Which drug is effective in eradicating the hypnozoite stage of Plasmodium vivax and Plasmodium ovale?
Which drug is effective in eradicating the hypnozoite stage of Plasmodium vivax and Plasmodium ovale?
What happens during the exoerythrocytic stage of the malaria life cycle?
What happens during the exoerythrocytic stage of the malaria life cycle?
Which drug type targets developing or dormant liver forms of parasites?
Which drug type targets developing or dormant liver forms of parasites?
Which of these drugs is classified as a quinoline derivative?
Which of these drugs is classified as a quinoline derivative?
What is the treatment of choice for giardiasis?
What is the treatment of choice for giardiasis?
What is a common adverse effect associated with pentamidine treatment?
What is a common adverse effect associated with pentamidine treatment?
What is a key limitation of iodoquinol in treating amebic infections?
What is a key limitation of iodoquinol in treating amebic infections?
Which drug is NOT suitable for treating late-stage trypanosomiasis with CNS involvement?
Which drug is NOT suitable for treating late-stage trypanosomiasis with CNS involvement?
What mechanism does pentamidine use to disrupt parasitic function?
What mechanism does pentamidine use to disrupt parasitic function?
What is the dosage of metronidazole for treating trichomoniasis?
What is the dosage of metronidazole for treating trichomoniasis?
Which of the following is NOT a common adverse effect of pentamidine?
Which of the following is NOT a common adverse effect of pentamidine?
What percentage of patients experience adverse effects when treated with pentamidine?
What percentage of patients experience adverse effects when treated with pentamidine?
What is one of the common side effects of mefloquine?
What is one of the common side effects of mefloquine?
Which antibiotic is known to target prokaryotic protein synthesis?
Which antibiotic is known to target prokaryotic protein synthesis?
What is the primary action of sulfadoxine in sulfonamide therapy?
What is the primary action of sulfadoxine in sulfonamide therapy?
How does atovaquone enhance proguanil's effect?
How does atovaquone enhance proguanil's effect?
Which of the following best describes the action of artemisinins?
Which of the following best describes the action of artemisinins?
What is the purpose of combining highly effective short-acting artemisinins with a longer-acting partner?
What is the purpose of combining highly effective short-acting artemisinins with a longer-acting partner?
What is the role of pyrimethamine in sulfonamide therapy?
What is the role of pyrimethamine in sulfonamide therapy?
Which combination is considered non-therapy because both components target the same pathway?
Which combination is considered non-therapy because both components target the same pathway?
Which of the following is NOT a common adverse effect associated with inhaled pentamidine?
Which of the following is NOT a common adverse effect associated with inhaled pentamidine?
What is the primary mechanism of action of benzimidazoles in treating helminth infections?
What is the primary mechanism of action of benzimidazoles in treating helminth infections?
Which of the following agents is considered the most toxic among the benzimidazoles?
Which of the following agents is considered the most toxic among the benzimidazoles?
What is the recommended initial treatment for a child diagnosed with acute falciparum malaria showing symptoms of severe disease?
What is the recommended initial treatment for a child diagnosed with acute falciparum malaria showing symptoms of severe disease?
Which symptom is indicative of potential complications during treatment with quinine for severe malaria?
Which symptom is indicative of potential complications during treatment with quinine for severe malaria?
What would suggest the need for prolonged treatment with benzimidazoles?
What would suggest the need for prolonged treatment with benzimidazoles?
Which of the following laboratory findings is consistent with severe falciparum malaria in the described case study?
Which of the following laboratory findings is consistent with severe falciparum malaria in the described case study?
In the context of treatment for helminth infections, a single dose of benzimidazoles is typically sufficient for which type of disease?
In the context of treatment for helminth infections, a single dose of benzimidazoles is typically sufficient for which type of disease?
What is the first line therapy for uncomplicated falciparum malaria?
What is the first line therapy for uncomplicated falciparum malaria?
Which of the following is not a recommended treatment for amebiasis in endemic areas?
Which of the following is not a recommended treatment for amebiasis in endemic areas?
Which drug is the treatment of choice for amebic colitis?
Which drug is the treatment of choice for amebic colitis?
Which of the following treatments is effective in curing uncomplicated liver abscesses caused by E. histolytica?
Which of the following treatments is effective in curing uncomplicated liver abscesses caused by E. histolytica?
What is the primary action of metronidazole in treating microbial infections?
What is the primary action of metronidazole in treating microbial infections?
Which drug class is effective against all tissue infections with E. histolytica when combined with a luminal amebicide?
Which drug class is effective against all tissue infections with E. histolytica when combined with a luminal amebicide?
Which of the following agents are luminal amebicides used to eradicate E. histolytica infections?
Which of the following agents are luminal amebicides used to eradicate E. histolytica infections?
In the treatment of extraintestinal infections caused by E. histolytica, which treatment is not recommended?
In the treatment of extraintestinal infections caused by E. histolytica, which treatment is not recommended?
Flashcards
Tissue schizonticides
Tissue schizonticides
Drugs that eliminate developing or dormant liver forms of the parasite.
Blood schizonticides
Blood schizonticides
Drugs that act on erythrocytic parasites, killing them in the blood.
Gametocides
Gametocides
Drugs that prevent transmission of the parasite to mosquitos by killing the gametocytes, the reproductive stage.
Exoerythrocytic Stage
Exoerythrocytic Stage
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Hypnozoite
Hypnozoite
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Causal Prophylactic Drugs
Causal Prophylactic Drugs
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Quinoline Derivatives
Quinoline Derivatives
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Radical Cure
Radical Cure
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Primaquine
Primaquine
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Chloroquine
Chloroquine
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Chloroquine's Limitations
Chloroquine's Limitations
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Chloroquine's Role in Prevention
Chloroquine's Role in Prevention
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Chloroquine Contraindications
Chloroquine Contraindications
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Lumefantrine
Lumefantrine
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Halofantrine
Halofantrine
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Quinine
Quinine
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Antifolates
Antifolates
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Pyrimethamine
Pyrimethamine
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Sulfadoxine
Sulfadoxine
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Sulfadoxine-pyrimethamine
Sulfadoxine-pyrimethamine
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Atovaquone-proguanil
Atovaquone-proguanil
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Atovaquone
Atovaquone
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Proguanil
Proguanil
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Artemisinins
Artemisinins
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First Line Therapy for Uncomplicated Falciparum Malaria
First Line Therapy for Uncomplicated Falciparum Malaria
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Pyronaridine Combination
Pyronaridine Combination
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Amebiasis
Amebiasis
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Diloxanide Furoate
Diloxanide Furoate
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Metronidazole for Amebic Colitis and Dysentery
Metronidazole for Amebic Colitis and Dysentery
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Metronidazole for Extraintestinal Amebiasis
Metronidazole for Extraintestinal Amebiasis
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Tinidazole: Mechanism of Action
Tinidazole: Mechanism of Action
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Metronidazole & Tinidazole: Limitations
Metronidazole & Tinidazole: Limitations
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Giardiasis Treatment
Giardiasis Treatment
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Trichomoniasis Treatment
Trichomoniasis Treatment
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Iodoquinol's Role
Iodoquinol's Role
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Pentamidine's Target
Pentamidine's Target
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Pentamidine's Risks
Pentamidine's Risks
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Pentamidine's Administration
Pentamidine's Administration
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Pentamidine's Long-Term Effects
Pentamidine's Long-Term Effects
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Suramin's Role
Suramin's Role
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Benzimidazoles
Benzimidazoles
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Albendazole
Albendazole
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Mebendazole
Mebendazole
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Thiabendazole
Thiabendazole
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Antimalarial Drugs
Antimalarial Drugs
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Falciparum Malaria
Falciparum Malaria
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Intravenous Artesunate
Intravenous Artesunate
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Intravenous Quinine
Intravenous Quinine
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Study Notes
Introduction to Antiprotozoal and Anthelmintic Drugs
- Parasites causing human disease fall into two main categories: unicellular protozoa and multicellular helminths.
- Protozoa have subgroups, primarily intestinal or extraintestinal.
- Helminths are subdivided into nematodes (roundworms), trematodes (flukes), and cestodes (tapeworms).
Malaria
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Four species of Plasmodium cause human malaria: P. falciparum, P. vivax, P. malariae, and P. ovale.
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Gametocytes develop in red blood cells before being taken up by mosquitoes, where they develop into infective sporozoites.
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The stages include liver stage (sporotzoites-hypnozoites-schizont-merozoites) and blood stage (merozoites-schizont-trophozoites-ring form-gametocytes).
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Important terms: blood schizonticides, tissue schizonticides, gametocides.
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Anopheles mosquito introduces Plasmodium sporozoites initiating infection.
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Parasites rapidly invade liver cells, the exoerythrocytic phase.
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Merozoites release from liver and infect red blood cells, the erythrocytic stage.
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Only erythrocytic parasites cause clinical illness.
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In P. falciparum and P. malariae infection, only one cycle of liver cell invasion occurs, ceasing spontaneously in less than 4 weeks. Treatment eliminating erythrocytic parasites is sufficient.
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In P. vivax and P. ovale infection, there is a dormant hepatic stage with hypnozoites which are not eradicated by most drugs; often needing two or more drugs to fully eradicate the infection.
Drug Classification
- Tissue schizonticides: Drugs that eliminate developing or dormant liver forms.
- Blood schizonticides: Drugs that act on red blood cells.
- Gametocides: Prevent transmission to mosquitoes; necessary for preventing spread to the insect vector.
- No single drug eradicates both hepatic and erythrocytic stages; often a combination of remedies is used
- Many drugs are causal prophylactic agents, capable of preventing erythrocytic infection before causing disease.
Drugs of Choice (Antimalarials)
- Quinoline Derivatives (e.g., chloroquine, amodiaquine, quinine, quinidine, mefloquine, primaquine, lumefantrine, halofantrine)
- Primaquine is the only medication used to eliminate hypnozoites
- Mechanism of Action (MOA) for Primaquine:
- Drugs accumulate in parasite food vacuoles, forming a complex with heme which prevents crystallization in Plasmodium food vacuoles.
- Heme polymerase activity is inhibited causing an accumulation of cytotoxic-free heme
Chloroquine
- Has been the drug of choice for treatment and chemoprophylaxis of malaria since the 1940s.
- Useful against sensitive P. falciparum and other species.
- Drug resistance has diminished its usefulness against P. falciparum.
- Replacing with artemisinin-based combination therapies most commonly.
- Remains preferred chemoprophylactic in regions without resistant P. falciparum malaria.
- Eradication of P. vivax and P. ovale requires a course of primaquine for hepatic stages.
Contraindications and Cautions
- Chloroquine: Contraindicated in patients with conditions it may worsen, including psoriasis, porphyria.
- Should be used cautiously in patients with retinal or visual field abnormalities, myopathy, liver, neurological, or hematologic disorders.
- Should not be co-administered with antidiarrheal agents kaolin or calcium- and magnesium-containing antacids.
- Considered safe in pregnancy and young children.
Quinine
- Exists in oral and parenteral forms.
Mefloquine
- Available as an oral formulation
- Used for treatment or prophylaxis of all susceptible malaria species; side effects can limit treatment/tolerability
Adverse Effects of Quinoline Derivatives
- QT prolongation
- Hypoglycemia
- Hemolysis in G6PD deficient patients
- Insomnia, vivid dreams, mood swings, depression, psychosis, and suicide
- Cinchonism (tinnitus, headache, nausea, and visual disturbances)
Antibiotics (e.g., Tetracycline, Doxycycline, Clindamycin)
- Used in conjunction with antimalarial drugs such as Quinine.
- Targets prokaryotic protein synthesis.
Antifolates (e.g., Sulfonamides, Pyrimethamine, Proguanil, Dapsone)
- Act synergistically to target enzymes involved in folate synthesis, a pathway required for parasite DNA synthesis.
- Sulfadoxine-pyrimethamine is a fixed-dose combination that acts on enzymes within the same pathway.
Atovaquone-proguanil
- Interferes with pyrimidine biosynthesis, essential for nucleic acid replication.
- Atovaquone blocks the parasite mitochondrial electron transport chain.
- Proguanil inhibits parasite DHFR (dihydrofolate reductase) through its active metabolite, cycloguanil.
- Proguanil may also act outside the folate pathway to enhance atovaquone toxicity.
Artemisinins (e.g., Artesunate)
- Act by binding iron bridges in heme leading to the generation of free radicals that damage parasite proteins, killing blood stages of all Plasmodium species, including gametocytes.
- Highly effective short-acting artemisinin combined with longer acting partners to protect against resistance; improving treatment convenience.
Lumefantrine & Pyronaridine
- Lumefantrine is available only as a fixed-dose combination with artemether
- Pyronaridine is now available in combination with artesunate
Amebiasis
- Infection with Entamoeba histolytica
- May present as asymptomatic intestinal infection, mild to moderate colitis, severe intestinal infection (dysentery), liver abscess, and extra-intestinal infections.
- Treatment choice is dependent on the clinical presentation.
Asymptomatic Intestinal Infection
- Carriers in endemic areas are usually not treated
- In non-endemic regions, treated with a luminal amebicide (diloxanide furoate, lodoquinol, paromomycin).
- Tissue amebicidal drug is unnecessary.
Amebic Colitis
- Treatment of choice: metronidazole plus a luminal amebicide
- Alternatives include tetracyclines and erythromycin for moderate colitis, but not effective against extra-intestinal disease.
- Other drugs (dehydroemetine, emetine) are best avoided due to toxicity.
Extraintestinal Infections
- Treatment of choice: metronidazole plus a luminal amebicide,
- A 10-day course of metronidazole cures in over 95% of uncomplicated liver abscesses.
- In unusual cases of treatment failure, aspiration of abscess, addition of chloroquine, or repeat metronidazole course may be necessary.
Metronidazole & Tinidazole
- Metronidazole or tinidazole are used for amebiasis
- Used to treat all tissue infections with Entamoeba histolytica; not for luminal (intestinal parasites)
- Must be used with a luminal amebicide
Giardiasis
- Metronidazole is the treatment of choice.
- Dosage is much lower for giardiasis than amebiasis.
- Efficacy is about 90% after a single treatment; tinidazole is equally effective.
Trichomoniasis
- Metronidazole is the treatment of choice.
- A single dose of 2g is effective.
- Metronidazole-resistance in organisms can lead to treatment failure; tinidazole may be effective for such organisms.
Iodoquinol
- A halogenated hydroxyquinoline, an effective luminal amebicide.
- Commonly used with metronidazole to treat amebic infections
Mechanism of Action (MOA) for Iodoquinol
- MOA is unknown against trophozoites.
- Effective against organisms in the bowel lumen, but not against trophozoites in the intestinal wall or extra-intestinal tissues.
Adverse Effects of Iodoquinol
- Infrequent: diarrhea, anorexia, nausea, vomiting, abdominal pain, headache, rash, and pruritus.
- May increase protein-bound serum iodine.
- Some halogenated hydroxy-quinolines can cause neurotoxicity with prolonged use at greater than recommended doses.
African Trypanosomiasis
Pentamidine
- Used for the early hemolymphatic stage of Trypanosoma brucei gambiense (West African sleeping sickness).
- Should not be used for late stage trypanosomiasis with CNS involvement.
Suramin
- Used for the treatment of early East African sleeping sickness.
Table 52-6: Treatment Choices for African Trypanosomiasis
- Provides detailed information regarding disease stages, first-line drugs, and alternative drugs for West and East African trypanosomiasis.
Mechanism of Action (MOA) for Pentamidine
- Pentamidine appears to bind to and disrupt the function of transfer RNA, leading to inhibition of protein synthesis.
Adverse Effects of Pentamidine
- Pentamidine is highly toxic with adverse effects in approximately 50% of patients receiving 4 mg/kg/day.
- Rapid IV administration may cause severe hypotension, tachycardia, dizziness, and dyspnea.
- Should be administered slowly over 2 hours; patients should be recumbent during treatment and closely monitored.
Adverse Effects of IM Pentamidine
- Pain at the injection site
- Sterile abscesses
- Pancreatic toxicity is common
- Hypoglycemia (often 5-7 days after treatment onset, lasting several weeks) which may be followed by hyperglycemia.
- Reversible renal insufficiency
Inhaler Pentamidine
- Generally well tolerated; but may cause cough, dyspnea, and bronchospasm.
Anthelmintic Drugs: Benzimidazoles
- Used primarily to treat infections caused by helminthes (e.g., common pinworms, pathogens causing massive cystic lesions in the brain).
- Agents: Albendazole, Mebendazole, Thiabendazole.
Mechanism of Action (MOA) for Benzimidazoles
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Interferes with elongation of the microtubules that are responsible for parasitic cellular structure; leading to a disruption of growth and division.
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Used to treat most intestinal worm infections (single dose); tissue invasive disease requires prolonged courses.
Case Study: Acute Falciparum Malaria
- A 5-year-old American girl presents with a fever, chills, and sweats, with additional symptoms of progressive disease. Recent travel to an endemic region suggests malaria.
- Laboratory tests showed signs of severe disease.
- Treatment should be commenced with intravenous artesunate, or intravenous quinine/quinidine if unavailable; closely monitored for neurologic, renal, and pulmonary complications; and have cardiac monitoring when utilizing quinine/quinidine.
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Description
Test your knowledge on the treatment and pharmacology of malaria in this comprehensive quiz. Questions cover drug mechanisms, contraindications, and the various stages of the malaria life cycle. Assess your understanding of both common and lesser-known aspects of malaria management.