Antiparasitic Drugs

Question 1

What stages of the malaria life cycle do quinolones affect?

Answer 1

Trophozoite, schizont, and gametocyte stages in blood vessels

Question 2

What are the pharmacokinetics of Quinolone derivatives?

Answer 2

• Quinine is PO and must take 3x a day
• Quinidine is IV but not used anymore

Question 3

What are clinical uses of derived quinolines?

Answer 3

Quinine: used for treatment of drug resistant P. falciparum infection
Quinidine: is used for severe malarial infection but discontinued

Question 4

What are adverse effects of quinoline derivatives?

Answer 4

• 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

Question 5

What is the MOA and clinical uses for chloroquine and hydroxychloroquine?

Answer 5

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

Question 6

What are adverse effects of chloroquine and hydroxychloroquine?

Answer 6

GI (n/v/d), QT prolongation, pruritus, visual disturbances
CIs: psoriasis or ocular disease

Question 7

What is the MOA

Question 8

What are clinical uses for mefloquine?

Answer 8

Prophylaxis (once week dosing) and treatment for drug resistant P. falciparum

Question 9

What are adverse effects for mefloquine?

Answer 9

GI (n/v/d), QT prolongation, vivid dreams (common), headache, anxiety, psychosis, seizures
CIs: epilepsy, psychosis, schizophrenia, depression, anxiety (all BBW)

Question 10

What are clinical uses for primaquine?

Answer 10

• 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

Question 11

What stages of the malaria life cycle does primaquine affect?

Answer 11

Stages in the hepatocytes where it is in the form of schizont, sporozoite, and hypnozoite

Question 12

What are adverse effects for primaquine?

Answer 12

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

Question 13

What drugs are artemisinin and/or derivatives?

Answer 13

Artesunate, artemether, and dihydroartemisinin
Characteristics: potent and acts fast so VERY effective and bonus bc many formulations

Question 14

What is the MOA of artemisinin and/or derivatives

Answer 14

Binds iron, breaks down peroxide bridges–> produces free radicals that can damage parasite

Question 15

What stages of the malaria life cycle do artemisinin and/or derivatives affect?

Answer 15

Affects trophozoite, schizont, and gametocyte stages in blood vessels

Question 16

What are clinical uses for artemisinin and/or derivatives?

Answer 16

• Treatment of uncomplicated falciparum malaria and used in combo (artemether-lumefantrine)
• Treatment of complicated falciparum malaria (artesunate and artemether)

Question 17

What are side effects of artemisinin and/or derivatives?

Answer 17

• GI (n/v/d), dizziness
  CIs: first trimester of pregnancy and children < 5kg

Question 18

What are general characteristics of antifolates?

Answer 18

• Used as combination regimens (atovaquone and proguanil aka Malarone)

Question 19

What antifolates are used for treatment of malaria?

Answer 19

Atovaquone and proguanil

Question 20

What is the MOA of malarone?

Answer 20

Atovaquone: disrupts mitochondrial electron transport in parasite and affects nucleotide synthesis
Proguanil: DHFR inhibitor

Question 21

What stage of the malaria life cycle does malarone affect?

Answer 21

Liver: schizont and sporozoite stages
Blood vessels: schizont and merozoite stages

Question 22

What are clinical uses of antifolates (malarone) and adverse effects?

Answer 22

• Used for treatment and prophylaxis of chloroquine resistant P. falciparum
• Adverse effects are abdominal pain, n/v/d, elevated liver enzymes
  CI: pregnancy

Question 23

What else can be used to treat and prevent malaria?

Answer 23

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

Question 24

Metronidazole clinical use

Answer 24

Treats amebiasis (w or w/o extraintestinal issues), giardiasis, and trichomoniasis

Question 25

Tinidazole clinical use

Answer 25

Amebiasis, giardiasis, and trichomoniasis

Question 26

Paromomycin (amninoglycoside) clinical use

Answer 26

Amebiasis (for asymp and together w metronidazole for intestinal disease) and giardiasis

Question 27

Iodoquinol clinical uses and special adverse effects

Answer 27

Used to treat Amebiasis and can have mild diarrhea and enlargement of thyroid

Question 28

T/F: Using paromomycin to treat giardiasis is safer in a pregnant patient

Answer 28

True

Question 29

Nitazoxanide clinical use and adverse effects

Answer 29

Giardiasis and can cause abdominal pain w diarrhea

Question 30

What drugs have a luminal action?

Answer 30

Paromomycin and iodoquinol

Question 31

What drug is a benzimidazole, how does it work, and what can it be used for?

Answer 31

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

Question 32

What are side effects seen in albendazole?

Answer 32

GI and elevation of liver enzymes CIs: pregnancy and hepatic disease

Question 33

What is the MOA, clinical use, and adverse effects for pyrantel pamoate?

Answer 33

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

Question 34

What is the MOA, clinical use, and adverse effects for ivermectin?

Answer 34

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

Question 35

What is the MOA, clinical use, and adverse effects for praziquantel?

Answer 35

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

Question 36

What MOA does albendazole have?

Answer 36

Starve the worm

Question 37

What MOA does ivermectin, pyrantel pamoate, and praziquantel share?

Answer 37

They all paralyze the worm