Anti-Parasitics Flashcards
Describe the major classes of antiparasitic agents: anti-helmminths
Benzimidazoles (Albendazole)
■ inhibit polymerization of worm B-tubulin
■ Active Metabolite well distributed to tissues
Avermectins (ivermectin)
■ potentiate the glutamate-gated chloride channels unique to nematodes
■ → toxic paralysis
■ (affects developing filarial worm larvae and prevents egress of microfilariae from the uterus of the adult worm)
Praziquantel (Biltricide, Distocide)
■ bimodal and dose dependent.:
■ Low: induces muscular activity and spastic worm paralysis
■ High: targets the worm tegument; causes Ca blebbing of the surface
● increase susceptibility to immune response
Describe the major classes of antiparasitic agents: anti-protozoals
Metronidazole
■ pro-drug: reduction at extra cyclic nitro group (preferentially occurs in anaerobic bacteria)
■ → highly reactive molecule that inflicts free radical damage on DNA and other macromolecules
List the major anti-malarials
Quinine Chloroquine Primaquine Mefloquine Chloroguanide Atavoquone Artemisinin
Explain the differences among blood schizonticides, tissue schizonticides, and
gametocytocides.
Blood schizonticides
○ includes most of the antimalarial drugs
○ act on the erythrocytic stage of the infection to block schizogeny and terminate a clinical attack (clinical cure)
○ for chemoprophylaxis by effecting a suppressive cure
Tissue schizonticides
2 types
■ Acts on the primary tissue schizonts within the liver to prevent initiation of clinical malaria (Chloroguanide)
■ Acts on the latent tissue forms to prevent relapse of P. vivax and P. ovale. (Primaquine)
Gametocytocides
○ Show activity against the sexual forms of the parasite; none used clinically
Albendazole
● Roundworms/Nematodes (Ascaris, Hookworms, Whipworms, Pinworms, Trichinosis [most effective early, before migration to muscle]
● Tapeworms/Cestodes: cysticercosis (pork tapeworms), Zoonotic tapeworms (Echinococcus granulosus and Echinococcus multilocularis) (often with surgical resection)
MOA:
■ inhibit polymerization of worm B-tubulin
■ Active Metabolite well distributed to tissues
NOT use if pregnant, cirrhosis
Ivermectin
● Roundworms/Nematodes (Threadworms, larvae of filarial worms, Threadworms, onchocerciasis)
MOA:
■ potentiate the glutamate-gated chloride channels unique to nematodes → toxic paralysis
■ (affects developing filarial worm larvae and prevents egress of microfilariae from the uterus of the adult worm) = kills larvae but not adult worms
NOT use if: compromised BBB (acted on by CNS P-glycoprotein efflux pumps)
Praziquantel
Tapeworms; all except echinococcosis and cysticercosis
○ Beef tapeworms, Pork tapeworms (incl: cysticercosis), Fish, Dwarf tapeworms,
Flukes: Blood flukes, Lung flukes, Liver flukes (C. sinenis and O. viverrini), Intestinal flukes
MOA: Increases cell membrane permeability, Ca- dependent, disintegrates schistosome integument
NOT use for nematodes
Metronidazole
■ pro-drug: reduction at extra cyclic nitro group (preferentially occurs in anaerobic bacteria)
■ → highly reactive molecule that inflicts free radical damage on DNA and other macromolecules
Uses: protozoa, T. vaginalis, amebiasis, giardia
Side effects: Headache, nausea, dry mouth, anorexia, diarrhea, cramping, neurotoxicity, do NOT combine with EtOH
Quinine
MOA
● Raises vacuolar pH, inhibiting polymerization of heme into hemozoin
Use
● Malaria, blood schizonticide, IV for cerebral malaria
Toxicity
● Cinchonism: ringing ears, headaches, nausea and blurred vision
● Hypersensitivity
Blackwater fever = severe form - massive hemolysis
● Hypoglycemia
● decreases the excitability of the motor end plate of skeletal muscle
Chloroquine
MOA
● Same MOA as quinine: Raises vacuolar pH, inhibiting polymerization of heme into hemozoin
● more effective and less toxic
● Resistance becoming widespread
Use
● Malaria, Blood schizonticide - chemoprophylaxis and treatment.
NOT use if: liver disease, G6PD deficiency
Toxicity
● high doses → CV effects (HTN and ECG abnormalities)
● Over 5 g can be lethal.
● Contraindicated in liver disease and G6PDH deficiency.
Primaquine
MOA
● Oxidative damage, gametocidal
Use
● latent tissue schizonts (chronic P. vivax and P. ovale)
NOT use if: G6PD deficiency, pregnant and breastfeeding women
Toxicity
● Methemoglobinemia
Mefloquine
MOA
● concentrated in food vacuoles, raises pH, and causes swelling, but it does not inhibit heme polymerization
● May form toxic complexes with heme
Use
● DOC: prophylaxis in regions of chloroquine resistance
● Given once weekly
● Treatment of chloroquine resistant malaria.
Toxicity
● Well tolerated, more SE when used as treatment
● Mild: nausea, dizziness, nightmares, fatigue, and lassitude
● Rare: Seizures and acute psychosis (contraindicated in those with psychiatric history)
● Decreases efficacy of oral typhoid vaccine
● Not approved for pregnant women
Chloroguanide
MOA
● Inhibits dihydrofolate reductase- thymidylate synthetase
Use
● Prophylaxis of malaria, active against tissue schizonts
● Can also terminate clinical attacks
● Combo with atovaquone = malarone
NOT use if: Pregnant or breastfeeding women, infants
Toxicity
● Very safe at therapeutic dose
Atavoquone
MOA
● Ubiquinone analog; selectively interfering with mitochondrial electron transport
Use
● prophylaxis and treatment of chloroquine-resistant malaria
● Used with chloroguanide = malarone
NOT use if: Pregnant or breastfeeding women, infants
Toxicity
● rash, fever, vomiting, diarrhea, and headache
● vomiting and diarrhea - from inadequate absorption
● 20% Dose-related maculopapular rash - does not become severe with continued therapy.
Artemisinin
(Qinghaosu)
MOA
● endoperoxide bridge or “warhead” is essential for activity
○ form a complex with ferrous non-heme iron
○ → formation of toxic, carbon-centered free radicals and alkylation of macromolecules
Use
● With lumefantrine for CQ-resistant malaria
○ single dose cures 90% of patients within 72 h
● Expensive so reserved for chloroquine-resistant and multidrug-resistant
Toxicity
● No dose-limiting toxicities in humans.
