Antiparasitic Drugs Flashcards
What stages of the malaria life cycle do quinolones affect?
Trophozoite, schizont, and gametocyte stages in blood vessels
What are the pharmacokinetics of Quinolone derivatives?
- Quinine is PO and must take 3x a day
- Quinidine is IV but not used anymore
What are clinical uses of derived quinolines?
Quinine: used for treatment of drug resistant P. falciparum infection
Quinidine: is used for severe malarial infection but discontinued
What are adverse effects of quinoline derivatives?
- GI effects (most common)
- Cardiac effects like QT prolongation (TdP)
- Cinchonism (tinnitus, headaches, dizziness)
- Acute hemolytic anemia (in pt w G6PD deficiency)
CIs: G6PD deficiency for quinine only
Interactions: inhibits CYP2D5 and PGP
What is the MOA and clinical uses for chloroquine and hydroxychloroquine?
MOA: similar to quinine and inhibits hem-polymerase activity leading to a toxic buildup of heme (same MOA for quinine, quinidine, and mefloquine)
Clinical uses: treatment and prophylaxis of non-resistant P. falciparum and P. malariae + can be used in combination w primaquine for eradication of hepatic stages of P. vivax and P. ovale
What are adverse effects of chloroquine and hydroxychloroquine?
GI (n/v/d), QT prolongation, pruritus, visual disturbances
CIs: psoriasis or ocular disease
What is the MOA
What are clinical uses for mefloquine?
Prophylaxis (once week dosing) and treatment for drug resistant P. falciparum
What are adverse effects for mefloquine?
GI (n/v/d), QT prolongation, vivid dreams (common), headache, anxiety, psychosis, seizures
CIs: epilepsy, psychosis, schizophrenia, depression, anxiety (all BBW)
What are clinical uses for primaquine?
- Active against hepatic stages of P. vivax and P. ovale (used in combo w chloroquine)
- Highly gametocidal against all 4 malaria species
- Only agent active against dormant hypnozoite stages
What stages of the malaria life cycle does primaquine affect?
Stages in the hepatocytes where it is in the form of schizont, sporozoite, and hypnozoite
What are adverse effects for primaquine?
GI, QT prolongation, hemolysis and hemolytic anemia (high risk if G6PD if deficient so must test) + counsel pts to look for dark colored urine
CIs: G6PD deficiency and pregnancy
Interactions: Induces CYP1A2 so caution w drugs like warfarin
What drugs are artemisinin and/or derivatives?
Artesunate, artemether, and dihydroartemisinin
Characteristics: potent and acts fast so VERY effective and bonus bc many formulations
What is the MOA of artemisinin and/or derivatives
Binds iron, breaks down peroxide bridges–> produces free radicals that can damage parasite
What stages of the malaria life cycle do artemisinin and/or derivatives affect?
Affects trophozoite, schizont, and gametocyte stages in blood vessels
What are clinical uses for artemisinin and/or derivatives?
- Treatment of uncomplicated falciparum malaria and used in combo (artemether-lumefantrine)
- Treatment of complicated falciparum malaria (artesunate and artemether)
What are side effects of artemisinin and/or derivatives?
- GI (n/v/d), dizziness
CIs: first trimester of pregnancy and children < 5kg
What are general characteristics of antifolates?
- Used as combination regimens (atovaquone and proguanil aka Malarone)
What antifolates are used for treatment of malaria?
Atovaquone and proguanil
What is the MOA of malarone?
Atovaquone: disrupts mitochondrial electron transport in parasite and affects nucleotide synthesis
Proguanil: DHFR inhibitor
What stage of the malaria life cycle does malarone affect?
Liver: schizont and sporozoite stages
Blood vessels: schizont and merozoite stages
What are clinical uses of antifolates (malarone) and adverse effects?
- Used for treatment and prophylaxis of chloroquine resistant P. falciparum
- Adverse effects are abdominal pain, n/v/d, elevated liver enzymes
CI: pregnancy
What else can be used to treat and prevent malaria?
Antibiotics like tetracycline, doxycycline, and clindamycin as they inhibit protein synthesis in parasite apicoplast (affects schizont and merozoite stage in blood vessel)
- Used alone for prophylaxis and in combo w quinine for tx
Metronidazole clinical use
Treats amebiasis (w or w/o extraintestinal issues), giardiasis, and trichomoniasis
Tinidazole clinical use
Amebiasis, giardiasis, and trichomoniasis
Paromomycin (amninoglycoside) clinical use
Amebiasis (for asymp and together w metronidazole for intestinal disease) and giardiasis
Iodoquinol clinical uses and special adverse effects
Used to treat Amebiasis and can have mild diarrhea and enlargement of thyroid
T/F: Using paromomycin to treat giardiasis is safer in a pregnant patient
True
Nitazoxanide clinical use and adverse effects
Giardiasis and can cause abdominal pain w diarrhea
What drugs have a luminal action?
Paromomycin and iodoquinol
What drug is a benzimidazole, how does it work, and what can it be used for?
Albendazole that is very broad spectrum but mainly GI helminths (nematodes) and cysticercosis or invasive cestodes
MOA: interferes w microtubule synthesis (inhibits cell replication) and microtubule-dependent glucose uptake
- Give w high fat meals
What are side effects seen in albendazole?
GI and elevation of liver enzymes
CIs: pregnancy and hepatic disease
What is the MOA, clinical use, and adverse effects for pyrantel pamoate?
MOA: neuromuscular blocking agent that increases Ach release and causes paralysis to the worm
Clinical use: intestinal helminths (roundworms, pinworm, hookworm)
Adverse effects: GI, dizziness, and elevation of liver enzymes
What is the MOA, clinical use, and adverse effects for ivermectin?
MOA: Increases Cl ions and causes hyperpol then death to parasite
Clinical use: severe intestinal nematodes (not hookworm)
Adverse effects: diarrhea, pruritus
CI in pregnancy
What is the MOA, clinical use, and adverse effects for praziquantel?
MOA: increased membrane permeability to calcium causes contraction which leads to paralysis
Clinical use: schistosomiasis (DOC), cysticercosis and many other intestinal tapeworms
Adverse effects: n/v/d, headache, dizziness, pruritus
What MOA does albendazole have?
Starve the worm
What MOA does ivermectin, pyrantel pamoate, and praziquantel share?
They all paralyze the worm
