Anti-malarial,antiprotozoal,and antihelmintic agents

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.

Antimalarial, Antiprotozoal, Antimalarial, Antiprotozoal, and Antihelmintic Agentsand Antihelmintic Agents


Protozoal InfectionsProtozoal Infections

Parasitic protozoa: live in or on humansParasitic protozoa: live in or on humans

• malariamalaria

• leishmaniasisleishmaniasis

• amebiasisamebiasis

• giardiasisgiardiasis

• trichomoniasistrichomoniasis


MalariaMalaria

• Caused by the plasmodium protozoa.Caused by the plasmodium protozoa.

• Four different plasmodium species.Four different plasmodium species.

• Cause: the bite of an infected adult Cause: the bite of an infected adult mosquito.mosquito.

• Can also be transmitted by infected Can also be transmitted by infected individuals via blood transfusion, individuals via blood transfusion, congenitally, or via infected needles by drug congenitally, or via infected needles by drug abusers.abusers.


Malarial Parasite (plasmodium)Malarial Parasite (plasmodium)

Two Interdependent Life CyclesTwo Interdependent Life Cycles

• Sexual cycle: in the mosquitoSexual cycle: in the mosquito

• Asexual cycle: in the humanAsexual cycle: in the human

– Knowledge of the life cycles is essential in Knowledge of the life cycles is essential in understanding antimalarial drug treatment.understanding antimalarial drug treatment.

– Drugs are only effective during the asexual cycle.Drugs are only effective during the asexual cycle.


Plasmodium Life CyclePlasmodium Life Cycle

Asexual cycle: two phasesAsexual cycle: two phases

• Exoerythrocytic phase:Exoerythrocytic phase: occurs “outside” occurs “outside” the erythrocytethe erythrocyte

• Erythrocytic phase:Erythrocytic phase: occurs “inside” occurs “inside” the erythrocytethe erythrocyte

Erythrocytes = RBCsErythrocytes = RBCs


Antimalarial AgentsAntimalarial Agents

Attack the parasite during the asexual phase, Attack the parasite during the asexual phase, when it is vulnerable when it is vulnerable

• Erythrocytic phase drugs: chloroquine, Erythrocytic phase drugs: chloroquine, hydroxychloroquine, quinine, mefloquinehydroxychloroquine, quinine, mefloquine

• Exoerythrocytic phase drug: primaquineExoerythrocytic phase drug: primaquine

May be used together for synergistic or additive killing power.May be used together for synergistic or additive killing power.


Antimalarials: Antimalarials: Mechanism of ActionMechanism of Action4-aminoquinoline derivatives chloroquine 4-aminoquinoline derivatives chloroquine

and hydroxychloroquineand hydroxychloroquine• Bind to parasite nucleoproteins and interfere with Bind to parasite nucleoproteins and interfere with

protein synthesis.protein synthesis.• Prevent vital parasite-sustaining substances from Prevent vital parasite-sustaining substances from

being formed.being formed.

• Alter pH within the parasite.Alter pH within the parasite.

• Interfere with parasite’s ability to metabolize andInterfere with parasite’s ability to metabolize anduse erythrocyte hemoglobin.use erythrocyte hemoglobin.

• Effective only during the erythrocytic phaseEffective only during the erythrocytic phase


Antimalarials: Mechanism of ActionAntimalarials: Mechanism of Action

4-aminoquinoline derivatives quinine and 4-aminoquinoline derivatives quinine and mefloquinemefloquine

• Alter pH within the parasite.Alter pH within the parasite.

• Interfere with parasite’s ability to metabolize and use Interfere with parasite’s ability to metabolize and use erythrocyte hemoglobin.erythrocyte hemoglobin.

• Effective only during the erythrocytic phase.Effective only during the erythrocytic phase.


Antimalarials: Mechanism of Action Antimalarials: Mechanism of Action

diaminophyrimidines pyrimethamine and diaminophyrimidines pyrimethamine and trimethoprimtrimethoprim

• Inhibit dihydrofolate reductase in the parasite.Inhibit dihydrofolate reductase in the parasite.

• This enzyme is needed by the parasite to make This enzyme is needed by the parasite to make essential substances.essential substances.

• Also blocks the synthesis of tetrahydrofolate.Also blocks the synthesis of tetrahydrofolate.

These agents may be used with sulfadoxine or dapsone These agents may be used with sulfadoxine or dapsone for synergistic effects.for synergistic effects.


Antimalarials: Mechanism of ActionAntimalarials: Mechanism of Action

primaquineprimaquine

• Only exoerythrocytic drug.Only exoerythrocytic drug.

• Binds and alters DNA.Binds and alters DNA.

sulfonamides, tetracyclines, clindamycinsulfonamides, tetracyclines, clindamycin

• Used in combination with antimalarials to increase Used in combination with antimalarials to increase protozoacidal effectsprotozoacidal effects


Antimalarials: Drug EffectsAntimalarials: Drug Effects

• Kill parasitic organisms.Kill parasitic organisms.

• Chloroquine and hydroxychloroquine also Chloroquine and hydroxychloroquine also have antiinflammatory effects.have antiinflammatory effects.


Antimalarials: Therapeutic UsesAntimalarials: Therapeutic Uses

• Used to kill plasmodium organisms, the Used to kill plasmodium organisms, the parasites that cause malaria.parasites that cause malaria.

• The drugs have varying effectiveness on The drugs have varying effectiveness on the different malaria organisms.the different malaria organisms.

• Some agents are used for prophylaxis Some agents are used for prophylaxis against malaria.against malaria.

• Chloroquine is also used for rheumatoid Chloroquine is also used for rheumatoid arthritis and lupus.arthritis and lupus.


Antimalarials: Side EffectsAntimalarials: Side Effects

• Many side effects for the various agentsMany side effects for the various agents

• Primarily gastrointestinal: nausea, vomiting, Primarily gastrointestinal: nausea, vomiting, diarrhea,diarrhea, anorexia, and abdominal painanorexia, and abdominal pain


AntiprotozoalsAntiprotozoals

• atovaquone (Mepron)atovaquone (Mepron)

• metronidazole (Flagyl)metronidazole (Flagyl)

• pentamidine (Pentam)pentamidine (Pentam)

• iodoquinol (Yodoxin, Di-Quinol)iodoquinol (Yodoxin, Di-Quinol)

• paromomycin (Humatin)paromomycin (Humatin)



• amebiasisamebiasis

• giardiasisgiardiasis

• pneumocystosispneumocystosis

• toxoplasmosistoxoplasmosis

• trichomoniasistrichomoniasis



TransmissionTransmission

• Person-to-personPerson-to-person

• Ingestion of contaminated water or foodIngestion of contaminated water or food

• Direct contact with the parasiteDirect contact with the parasite

• Insect bite (mosquito or tick)Insect bite (mosquito or tick)


Antiprotozoals: Mechanism of Action Antiprotozoals: Mechanism of Action

and Uses atovaquone (Mepron)and Uses atovaquone (Mepron)• Protozoal energy comes from the Protozoal energy comes from the

mitochondriamitochondria

• Atovaquone: selective inhibition of Atovaquone: selective inhibition of mitochondrial electron transportmitochondrial electron transport

• Result: no energy, leading to cellular deathResult: no energy, leading to cellular death

Used to treat mild to moderate P. carinii Used to treat mild to moderate P. carinii


Antiprotozoals: Mechanism of Action Antiprotozoals: Mechanism of Action and Uses metronidazoleand Uses metronidazole

• Disruption of DNA synthesis as well as Disruption of DNA synthesis as well as nucleic acid synthesisnucleic acid synthesis

• Bactericidal, amebicidal, trichomonacidalBactericidal, amebicidal, trichomonacidal

Used for treatment of trichomoniasis, amebiasis, Used for treatment of trichomoniasis, amebiasis, giardiasis, anaerobic infections, and antibiotic-giardiasis, anaerobic infections, and antibiotic-associated pseudomembranous colitisassociated pseudomembranous colitis


Antiprotozoals: Mechanism of Action Antiprotozoals: Mechanism of Action and Uses pentamidineand Uses pentamidine

• Inhibits DNA and RNAInhibits DNA and RNA

• Binds to and aggregates ribosomesBinds to and aggregates ribosomes

• Directly lethal to Pneumocystis cariniiDirectly lethal to Pneumocystis carinii

• Inhibits glucose metabolism, protein and RNA Inhibits glucose metabolism, protein and RNA synthesis, and intracellular amino acid synthesis, and intracellular amino acid transporttransport

Mainly used to treat P. carinii pneumonia Mainly used to treat P. carinii pneumonia and other protozoal infectionsand other protozoal infections


Antiprotozoals: Mechanism of Action Antiprotozoals: Mechanism of Action and Uses iodoquinol (Yodoxin, Di-Quinol)and Uses iodoquinol (Yodoxin, Di-Quinol)

• ““Luminal” or “contact” amebicideLuminal” or “contact” amebicide

• Acts primarily in the intestinal lumen of the Acts primarily in the intestinal lumen of the infected hostinfected host

• Directly kills the protozoaDirectly kills the protozoa

Used to treat intestinal amebiasisUsed to treat intestinal amebiasis


Antiprotozoals: Mechanism of Action Antiprotozoals: Mechanism of Action and Uses paromomycinand Uses paromomycin

• ““Luminal” or “contact” amebicideLuminal” or “contact” amebicide

• Kills by inhibiting protein synthesisKills by inhibiting protein synthesis

Used to treat amebiasis and intestinal protozoal Used to treat amebiasis and intestinal protozoal infections, and also adjunct therapy in infections, and also adjunct therapy in management of hepatic comamanagement of hepatic coma


Antiprotozoals: Side EffectsAntiprotozoals: Side Effects

atovaquoneatovaquone• nausea, vomiting, diarrhea, anorexianausea, vomiting, diarrhea, anorexia

metronidazolemetronidazole• metallic taste, nausea, vomiting, diarrhea, metallic taste, nausea, vomiting, diarrhea,

abdominal crampsabdominal cramps

iodoquinoliodoquinol• nausea, vomiting, diarrhea, anorexia, nausea, vomiting, diarrhea, anorexia,

agranulocytosisagranulocytosis


Antiprotozoals: Side EffectsAntiprotozoals: Side Effects

pentamidinepentamidine

• bronchospasms, leukopenia, thrombocytopenia, bronchospasms, leukopenia, thrombocytopenia, acute pancreatitis, acute renal failure, increased liver acute pancreatitis, acute renal failure, increased liver function studiesfunction studies

paromomycinparomomycin

• nausea, vomiting, diarrhea, stomach crampsnausea, vomiting, diarrhea, stomach cramps


AntihelminticsAntihelmintics

• diethylcarbamazine (Hetrazan)diethylcarbamazine (Hetrazan)• mebendazole (Vermox)mebendazole (Vermox)• niclosamide (Niclocide)niclosamide (Niclocide)• oxamniquine (Vansil)oxamniquine (Vansil)• piperazine (Vermizine)piperazine (Vermizine)• praziquantel (Biltricide)praziquantel (Biltricide)• pyrantel (Antiminth)pyrantel (Antiminth)• thiabendazole (Mintezol)thiabendazole (Mintezol)



• Drugs used to treat parasitic worm infections: Drugs used to treat parasitic worm infections: helmintic infections helmintic infections

• Unlike protozoa, helminths are large and Unlike protozoa, helminths are large and have complex cellular structureshave complex cellular structures

• Drug treatment is very specificDrug treatment is very specific



• It is VERY IMPORTANT to identify the It is VERY IMPORTANT to identify the causative wormcausative worm

• Done by finding the parasite ova or larvae in Done by finding the parasite ova or larvae in feces, urine, blood, sputum, or tissue feces, urine, blood, sputum, or tissue

– cestodes (tapeworms)cestodes (tapeworms)

– nematodes (roundworms)nematodes (roundworms)

– trematodes (flukes)trematodes (flukes)


Antihelmintics: Mechanism of Action Antihelmintics: Mechanism of Action and Usesand Uses

diethylcarbamazine (Hetrazan)diethylcarbamazine (Hetrazan)• Inhibits rate of embryogenesisInhibits rate of embryogenesis

thiabendazole (Mintezol)thiabendazole (Mintezol)• Inhibits the helminth-specific enzyme, fumarate Inhibits the helminth-specific enzyme, fumarate

reductasereductase

Both used for nematodes Both used for nematodes (tissue and some roundworms)(tissue and some roundworms)


Antihelmintics: Mechanism of ActionAntihelmintics: Mechanism of Action

piperazine (Vermizine) and pyrantel (Antiminth)piperazine (Vermizine) and pyrantel (Antiminth)

• Blocks acetylcholine at the neuromuscular junction, Blocks acetylcholine at the neuromuscular junction, resulting in paralysis of the worms, which are then resulting in paralysis of the worms, which are then expelled through the GI tractexpelled through the GI tract

Used to treat nematodes (giant worm and pinworm)Used to treat nematodes (giant worm and pinworm)



mebendazole (Vermox)mebendazole (Vermox)

• Inhibits uptake of glucose and other nutrients, Inhibits uptake of glucose and other nutrients, leading to autolysis and death of the parasitic wormleading to autolysis and death of the parasitic worm

Used to treat cestodes and nematodesUsed to treat cestodes and nematodes



niclosamide (Niclocide)niclosamide (Niclocide)

• Causes the worm to become dislodged Causes the worm to become dislodged from the GI wallfrom the GI wall

• They are then digested in the intestines They are then digested in the intestines and expelledand expelled

Used to treat cestodesUsed to treat cestodes



oxamniquine (Vansil) and praziquantel oxamniquine (Vansil) and praziquantel (Biltricide)(Biltricide)

• Cause paralysis of worms’ musculature and Cause paralysis of worms’ musculature and immobilization of their suckersimmobilization of their suckers

• Cause worms to dislodge from mesenteric veins Cause worms to dislodge from mesenteric veins to the liver, then killed by host tissue reactionsto the liver, then killed by host tissue reactions

Used to treat trematodes, cestodes Used to treat trematodes, cestodes (praziquantel only)(praziquantel only)


Antihelmintics: Side EffectsAntihelmintics: Side Effects

niclosamide, oxamniquine, praziquantel, niclosamide, oxamniquine, praziquantel, thiabendazole, piperazine, pyrantelthiabendazole, piperazine, pyrantel

• nausea, vomiting, diarrhea, dizziness, headachenausea, vomiting, diarrhea, dizziness, headache

mebendazolemebendazole

• diarrhea, abdominal pain, tissue necrosisdiarrhea, abdominal pain, tissue necrosis


Antimalarial, Antiprotozoal, Antihelmintic Antimalarial, Antiprotozoal, Antihelmintic Agents: Nursing ImplicationsAgents: Nursing Implications

• Before beginning therapy, perform a Before beginning therapy, perform a thorough health history and medication thorough health history and medication history, and assess for allergies.history, and assess for allergies.

• Check baseline VS.Check baseline VS.

• Check for conditions that may contraindicate Check for conditions that may contraindicate use, and for potential drug interactions.use, and for potential drug interactions.



• Some agents may cause the urine to have an Some agents may cause the urine to have an asparagus-like odor, or cause an unusual asparagus-like odor, or cause an unusual skin odor, or a metallic taste; be sure to skin odor, or a metallic taste; be sure to warn the patient ahead of time.warn the patient ahead of time.

• Administer ALL agents as ordered and for Administer ALL agents as ordered and for the prescribed length of time.the prescribed length of time.

• Most agents should be taken with food to Most agents should be taken with food to reduce GI upset.reduce GI upset.


Antimalarial Agents: Antimalarial Agents: Nursing ImplicationsNursing Implications

• Assess for presence of malarial symptoms.Assess for presence of malarial symptoms.

• When used for prophylaxis, these agents When used for prophylaxis, these agents should be started 2 weeks before potential should be started 2 weeks before potential exposure to malaria, and for 8 weeks after exposure to malaria, and for 8 weeks after leaving the area.leaving the area.

• Medications are taken weekly, with 8 ounces Medications are taken weekly, with 8 ounces of water.of water.


Antimalarial Agents: Antimalarial Agents: Nursing ImplicationsNursing Implications

• Instruct patient to notify physician Instruct patient to notify physician immediately if ringing in the ears, hearing immediately if ringing in the ears, hearing decrease, visual difficulties, nausea, decrease, visual difficulties, nausea, vomiting, profuse diarrhea, or abdominal pain vomiting, profuse diarrhea, or abdominal pain occur.occur.

• Alert patients to the possible recurrence of Alert patients to the possible recurrence of the symptoms of malaria so that they will the symptoms of malaria so that they will know to seek immediate treatment.know to seek immediate treatment.



Monitor for side effects:Monitor for side effects:

• Ensure that patients know the side effects that Ensure that patients know the side effects that should be reported.should be reported.

• Monitor for therapeutic effects and adverse effects Monitor for therapeutic effects and adverse effects with long-term therapy.with long-term therapy.

Education

Anti-malarial,antiprotozoal,and antihelmintic agents