antiparisitic drugs Flashcards

Question

kinetoplastid parasites

Answer 1

Leishmania African trypanosomes -Trypanosoma brucei gambiense – West African trypanosomiasis – accounts for 95% of cases -Trypanosoma brucei rhodesiense– East African trypanosomiasis – accounts for 5% of cases American trypanosomes - Trypanosoma cruzi Share common features -Unique organelles - kinetoplast, glycosome -Distinct mechanisms of gene expression

Answer 2

At risk: 350 million people, 88 countries 12 million people infected Annual incidence: 2 million Transmitted by sandflies Intracellular parasite - Replicates in phagolysosome

Answer 3

Found in 34 countries; most common in southern Europe and Brazil Immunocompromised people unable to control leishmania infections Accelerating spread of visceral leishmaniasis leishmaniasis accelerates the onset of AIDS by cumulative immunosuppression and by stimulating replication of the virus IV drug users at greatest risk Different patterns of drug susceptibility

Answer 4

African sleeping sickness - Fatal if untreated Extracellular parasite - Trypanosoma brucei - Initial phase - hemolymphatic; Late phase - CNS ~ 20,000 cases in 2015 Transmitted by tsetse fly Avoids immune response by changing coat protein

Answer 5

Also called Chaga’s disease Trypanosoma cruzi Endemic in Latin America - Mexico, Central and S. America; 6-8 million people infected (2015); 300,000 in U.S. (no transmission) Transmitted by reduviid bugs - Blood transfusion Intracellular - Replicates in cytoplasm

Answer 6

Leishmaniasis - Sodium stibogluconate or Amphotericin B; Alternatives - pentamidine or miltefosine African trypanosomiasis - Early stage - pentamidine (West) or Suramin (East); Late stage - Melarsoprol (East and West) or Eflornithine (West; combination with nifurtimox is promising)) American trypanosomiasis - Nifurtimox or Benznidazole

Answer 7

Most commonly used drugs for T. cruzi; also used incombo therapy for T. brucei Mechanism unknown - activated by a NADH-dependent mitochondrial nitroreductase; generation of nitro radical anions Reduces severity of acute phase - Eliminates parasite in 80% of acute infections and ~50% of chronic infections; Does not reverse tissue damage in chronic infections Orally available - 3-4 month course of treatment Toxicity common - hypersensitivity, GI complications - Leads to premature stoppage of treatment

Answer 8

``` Entamoeba histolytica (amebiasis) - 50 million cases per year; 40,000 to 110,000 deaths; 1 - 2 % of US population Giardia lamblia (giardiasis) - One of the most common water- borne diseases in U.S.; 5% of US population Trichomonas vaginalis - Sexually transmitted; 200 million cases per year; 20 -25 % of women in US ```

Answer 9

Poor sanitation and fecal contamination of food and water promote spread Can occur any where - More common in Latin America, Africa, and the Indian subcontinent Initially infects the intestine - Sometimes reaches other organs, such as the liver Most infections are asymptomatic Symptoms include diarrhea, increased flatulence, abdominal cramps - Some people develop liver abscesses

Answer 10

Diarrheal disease - Infections range from asymptomatic to severe diarrhea & malabsorption Treatment of choice: metronidazole; Nitazoxanide

Answer 11

300,000 infections per year in the U.S. Most frequent cause of recreational water-related disease outbreaks Most common symptom is watery diarrhea Other symptoms: Stomach cramps or pain, Dehydration, Nausea & vomiting, Fever, Weight loss More serious illness in immunocompromised people Drug of choice: Nitazoxanide***

Answer 12

Resides in the female lower genital tract and the male urethra and prostate Frequently symptomatic in women - Vaginitis with a purulent discharge; vulvar and cervical lesions, abdominal pain, dysuria and dyspareunia Frequently asymptomatic in men

Answer 13

Drug of choice for extraintestinal Entamoeba histolytica, giardiasis and trichomoniasis Kills trophozoites but not cysts Treatment usually followed by luminal drug to eliminate asymptomatic infection Mechanism not definitively known - Anaerobes have electron transport proteins with low redox potential – activate metronidazole Tinidazole is a similar drug with less toxicity

Answer 14

Drugs for intestinal forms: - Paromomycin: Aminoglycoside; Not significantly absorbed in GI tract; Only used as an intestinal amebicide; Similar efficacy and less toxic than other drugs; Also active against Cryptosporidium - Iodoquinol: Alternative to paromomycin; Commonly used in combination with metronidazole; Mechanism unknown

Answer 15

rapidly metabolized to the active metabolite (tizoxanide) Mechanism uncertain - interferes with pyruvate:ferredoxin oxidoreductase (PFOR) enzyme-dependent electron transfer reaction; Inhibits anaerobic metabolism inhibits the growth of sporozoites and oocysts of Cryptosporidium parvum and trophozoites of Giardia lamblia

Answer 16

Worm infections: ~25% of the world’s population is infected; ~15% of the U.S. population is infected Worms have unique biology: Multiply outside of their definitive host in contrast to other parasites; Evade immune system - Infections are chronic - last for the lifetime of host

Answer 17

``` Beef Tapeworm (Taenia saginata) - Global distribution; Transmitted by eating undercooked meat Pork Tapeworm (Taenia solium) - Global distribution; Bladders worms; Occasionally found in uncooked pork Fish Tapeworm (Diphyllobothrium latum) - Largest tapeworm - can reach 10 m in length; Transmitted by eating undercooked fish; Northern hemisphere; Rob host of nutrients, especially vitamin B12 ```

Answer 18

Dog Tapeworm Dogs are definitive hosts Humans are an intermediate hosts for larval forms of Echinococcus species - cause "cystic” (E. granulosus) and "alveolar" (E. multilocularis and E. vogeli) hydatid disease; Parasite eggs from canine stools are a major cause of disease; produces slowly growing cysts usually in liver and lung Preferred treatment - Removal of the cysts by surgery - Prolonged regimens of albendazole - some patients are not cured despite multiple courses of therapy; lifelong therapy may be required.

Answer 19

Caused by autoinfection by ingesting eggs produced by T. solium After ingestion, oncospheres hatch in the intestine, invade the intestinal wall, and migrate to striated muscles (and brain, liver, and other tissues) Develop into cysticerci • Can cause serious disease in the brain (neurocysticercosis)

Answer 20

Most common cestode infections Can be transmitted directly between humans 3 - 4 cm in length Found in temperate regions worldwide Children predominantly infected Infected by ingesting eggs Generally not serious, but chronic infections can cause more severe symptoms

Answer 21

``` Bloodflukes appear w big bellies Three species infect humans: Schistosoma hematobium, Schistosoma mansoni, Schistosoma japonicum 200 million people infected worldwide Caribbean, S. America, Africa, Mid East Snails are intermediate host Can live for 5 - 10 years in host symptoms due to immune reaction to eggs - Headaches, fatigue, fever, gastrointestinal problems; Hepatic fibrosis and ascites; Bladder cancer ```

Answer 22

Drug therapy for helminths Broad spectrum activity Three currently on the market: -Mebendazole; 1st in this class -Thiabendazole; Toxicity limits use -Albendazole; Useful against both GI and tissue infections Mechanism of action - Binds to tubulin; Inhibits formation of microtubules - Microtubules grow from “plus” end; Benzimidazoles cap microtubules; Microtubules continue to be shortened from minus end Can bind to mammalian tubulin - Reason for specificity not clear

Answer 23

Drug of choice for cysticercosis Variable absorption Rapidly converted to albendazole sulfoxide – active metabolite Also used for pinworms, hookworms, ascariasis, trichuriasis, and strongyloidiasis

Answer 24

Used for pinworms, hookworms, ascariasis, and trichuriasis

Answer 25

Highly effective against cestodes and trematodes - No activity against nematodes Mechanism of action -At lower concentrations - increased muscular activity - contraction and spastic paralysis; worms detach from blood vessel walls; migrate from the mesenteric veins to the liver -At higher concentrations - tegumental damage and exposes a number of tegumental antigens -May also disrupt calcium homeostasis therapeutic uses: -Drug of choice for all forms of schistosomiasis - Two or three doses yield high cure rates; Dramatically reduces egg burden in those not cured; Used in mass treatment programs -Single dose kills 100% of T. saginata, T. solium, and D. latum - Does not kill eggs of T. solium -toxicity: Mild and transient adverse effects are common; More severe reaction to dying worms

Answer 26

Drug of choice for strongyloidiasis and onchocerciasis Semisynthetic macrocyclic lactone Mechanism of action: -Paralyzes microfilariae -binds to glutamate-activated Cl− channels found in nematode nerve or muscle cells -causes hyperpolarization by increasing intracellular chloride concentration -also binds with high affinity to γ-aminobutyric acid (GABA)-gated and other ligand-gated Cl−channels -Allows host cytotoxic cells to adhere -Does not kill adult worms -Blocks release of progeny Therapeutic uses: -Primarily used to treat onchocerciasis -Single dose -Used in mass treatment programs - once a year - Treatment must be continued for lifespan of adult worm -Also used for: Ascariasis, Enterobiasis, Strongyloidiasis, Filariasis

Answer 27

Broad-spectrum antihelminth Available over the counter Highly effective for treatment of pinworms and ascaris Moderately effective against hookworms Active against adult and immature worms - Not active against migratory stages or ova Mechanism of action: Depolarizing Neuromuscular blocking agent; Causes release of acetylcholine and inhibition of cholinesterase; Worms are paralyzed & expelled Clinical uses: Ascariasis - one dose (11 mg/kg) is 85 - 100 % effective; Pinworms - two doses two weeks apart - 95% cure rate Adverse effects are mild and infrequent

Answer 28

Mechanism unknown – requires host components Drug of choice for filariasis and loiasis - Microfilariae are rapidly killed; Adults are killed more slowly Well absorbed from GI tract Generally well-tolerated Reactions to dying worms can be severe - May also lead to systemic inflammation from release of bacterial endosymbiont

Answer 29

filarial parasites harbor bacterial symbionts of the genus Wolbachia doxycycline kills Wolbachia adult female Onchocerca worms become sterile