Malaria Treatment and Pharmacology Quiz
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Questions and Answers

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?

  • Inhibiting RNA synthesis
  • Disrupting mitochondrial function
  • Forming complexes with heme to prevent crystallization (correct)
  • Blocking folate metabolism

    • 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?

    <p>Chloroquine is safe to use in pregnancy.</p> Signup and view all the answers

    Which of the following treatments can lead to hypoglycemia as a side effect?

    <p>Quinine</p> Signup and view all the answers

    What is the preferred chemoprophylactic agent in areas where there is no resistant P falciparum malaria?

    <p>Chloroquine</p> Signup and view all the answers

    Which drug can be used both for treatment and prophylaxis of malaria?

    <p>Mefaloquine</p> Signup and view all the answers

    Which side effect is common across all quinoline derivatives?

    <p>QT prolongation</p> Signup and view all the answers

    What type of organisms are classified as helminths?

    <p>Multicellular roundworms, flukes, and tapeworms</p> Signup and view all the answers

    Which species of Plasmodium is not recognized for causing malaria in humans?

    <p>Plasmodium knowlesi</p> Signup and view all the answers

    What is the role of gametocides in malaria treatment?

    <p>To prevent transmission of the parasite to mosquitoes</p> Signup and view all the answers

    What do blood schizonticides specifically target?

    <p>Erythrocytic parasites causing clinical illness</p> Signup and view all the answers

    Which drug is effective in eradicating the hypnozoite stage of Plasmodium vivax and Plasmodium ovale?

    <p>Primaquine</p> Signup and view all the answers

    What happens during the exoerythrocytic stage of the malaria life cycle?

    <p>Merozoites invade liver cells</p> Signup and view all the answers

    Which drug type targets developing or dormant liver forms of parasites?

    <p>Tissue schizonticides</p> Signup and view all the answers

    Which of these drugs is classified as a quinoline derivative?

    <p>Amodiaquine</p> Signup and view all the answers

    What is the treatment of choice for giardiasis?

    <p>Metronidazole</p> Signup and view all the answers

    What is a common adverse effect associated with pentamidine treatment?

    <p>Severe hypotension</p> Signup and view all the answers

    What is a key limitation of iodoquinol in treating amebic infections?

    <p>Ineffective against intestinal wall trophozoites</p> Signup and view all the answers

    Which drug is NOT suitable for treating late-stage trypanosomiasis with CNS involvement?

    <p>Pentamidine</p> Signup and view all the answers

    What mechanism does pentamidine use to disrupt parasitic function?

    <p>Inhibition of protein synthesis</p> Signup and view all the answers

    What is the dosage of metronidazole for treating trichomoniasis?

    <p>2 g</p> Signup and view all the answers

    Which of the following is NOT a common adverse effect of pentamidine?

    <p>Urinary retention</p> Signup and view all the answers

    What percentage of patients experience adverse effects when treated with pentamidine?

    <p>About 50%</p> Signup and view all the answers

    What is one of the common side effects of mefloquine?

    <p>Insomnia</p> Signup and view all the answers

    Which antibiotic is known to target prokaryotic protein synthesis?

    <p>Doxycycline</p> Signup and view all the answers

    What is the primary action of sulfadoxine in sulfonamide therapy?

    <p>Acts on dihydropteroate synthase</p> Signup and view all the answers

    How does atovaquone enhance proguanil's effect?

    <p>By enhancing mitochondrial membrane toxicity</p> Signup and view all the answers

    Which of the following best describes the action of artemisinins?

    <p>Bind iron and generate free radicals</p> Signup and view all the answers

    What is the purpose of combining highly effective short-acting artemisinins with a longer-acting partner?

    <p>Protect against artemisinin resistance</p> Signup and view all the answers

    What is the role of pyrimethamine in sulfonamide therapy?

    <p>Inhibits dihydrofolate reductase</p> Signup and view all the answers

    Which combination is considered non-therapy because both components target the same pathway?

    <p>Sulfadoxine and Pyrimethamine</p> Signup and view all the answers

    Which of the following is NOT a common adverse effect associated with inhaled pentamidine?

    <p>Rash</p> Signup and view all the answers

    What is the primary mechanism of action of benzimidazoles in treating helminth infections?

    <p>Interference with microtubule elongation</p> Signup and view all the answers

    Which of the following agents is considered the most toxic among the benzimidazoles?

    <p>Thiabendazole</p> Signup and view all the answers

    What is the recommended initial treatment for a child diagnosed with acute falciparum malaria showing symptoms of severe disease?

    <p>Intravenous artesunate</p> Signup and view all the answers

    Which symptom is indicative of potential complications during treatment with quinine for severe malaria?

    <p>Cardiac arrhythmias</p> Signup and view all the answers

    What would suggest the need for prolonged treatment with benzimidazoles?

    <p>Massive cystic lesions in the brain</p> Signup and view all the answers

    Which of the following laboratory findings is consistent with severe falciparum malaria in the described case study?

    <p>Bilirubin elevation</p> Signup and view all the answers

    In the context of treatment for helminth infections, a single dose of benzimidazoles is typically sufficient for which type of disease?

    <p>Intestinal worm infections</p> Signup and view all the answers

    What is the first line therapy for uncomplicated falciparum malaria?

    <p>Lumefantrine and artemether</p> Signup and view all the answers

    Which of the following is not a recommended treatment for amebiasis in endemic areas?

    <p>Antibiotic therapy with tetracyclines</p> Signup and view all the answers

    Which drug is the treatment of choice for amebic colitis?

    <p>Metronidazole plus a luminal amebicide</p> Signup and view all the answers

    Which of the following treatments is effective in curing uncomplicated liver abscesses caused by E. histolytica?

    <p>Metronidazole plus a luminal amebicide</p> Signup and view all the answers

    What is the primary action of metronidazole in treating microbial infections?

    <p>Disrupting DNA of microbial cells</p> Signup and view all the answers

    Which drug class is effective against all tissue infections with E. histolytica when combined with a luminal amebicide?

    <p>Metronidazole or Tinidazole</p> Signup and view all the answers

    Which of the following agents are luminal amebicides used to eradicate E. histolytica infections?

    <p>Paromomycin</p> Signup and view all the answers

    In the treatment of extraintestinal infections caused by E. histolytica, which treatment is not recommended?

    <p>Use of iodoquinol alone</p> Signup and view all the answers

    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

    • Four species of Plasmodium cause human malaria: P. falciparum, P. vivax, P. malariae, and P. ovale.

    • Gametocytes develop in red blood cells before being taken up by mosquitoes, where they develop into infective sporozoites.

    • The stages include liver stage (sporotzoites-hypnozoites-schizont-merozoites) and blood stage (merozoites-schizont-trophozoites-ring form-gametocytes).

    • Important terms: blood schizonticides, tissue schizonticides, gametocides.

    • Anopheles mosquito introduces Plasmodium sporozoites initiating infection.

    • Parasites rapidly invade liver cells, the exoerythrocytic phase.

    • Merozoites release from liver and infect red blood cells, the erythrocytic stage.

    • Only erythrocytic parasites cause clinical illness.

    • 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.

    • 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

    • Interferes with elongation of the microtubules that are responsible for parasitic cellular structure; leading to a disruption of growth and division.

    • 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.

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