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5200: Structural Integrity > Jacobs Pharm II: Worms, Lice, Scabies, Protozoans > Flashcards

Jacobs Pharm II: Worms, Lice, Scabies, Protozoans Flashcards

1
Q
A
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2
Q

Name the organism also known as “giant intestinal roundworm”

A

Ascaris (infection= ascariasis)

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3
Q

Name the organism that causes pinworm.

A

Enterobius

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4
Q

Name two organisms that cause hookworm infections.

A

Necator and Ancylostoma

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5
Q

Name the organism that causes whipworm.

A

Thichuris

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6
Q

Name the organism commonly known as a “blood fluke”

A

Schistosoma

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7
Q

Name the organism commonly known as the “Chinese liver fluke”

A

Clonorchis

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8
Q

Name the organism commonly known as the “common liver fluke” aka. “sheep liver fluke”

A

Fasciola

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9
Q

Name the organism better known as “beef tapeworm” or “pork tapeworm”

A

Taenia

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10
Q

Which organism causes cysticercosis?

A

Pork tapeworms (Taenia)

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11
Q

Which organism causes hydatid disease, and is transmitted from infected dogs (or other hosts, like sheep)?

A

Echinococcus

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12
Q

Name 3 drug options for Enterobius (pinworm) infections.

A
  • pyrantel pamoate
  • mebendazole
  • albendazole
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13
Q

Name 2 drug options for MOST roundworm infections (excluding threadworm or filariasis).

A
  • albendazole
  • mebendazole
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14
Q

Name the drug of choice for treating threadworm infections or filariasis.

A

ivermectin

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15
Q

Name the drug of choice for treating blood fluke and Chinese liver flukes.

A

praziquantel

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16
Q

Name two drugs of choice for treating sheep liver fluke (Fasciola) infections.

A
  • triclabendazole
  • nitazoxanide
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17
Q

Name two drugs of choice for treating non-cyst tapeworm infections (i.e. not cysticercosis).

A
  • praziquantel
  • niclosamide
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18
Q

What is the drug of choice for treating cyst forms of tapeworm (cysticercosis, or hydatid disease)?

A

albendazole

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19
Q

Name three anthelmintic drugs that inhibit microtubules.

A
  • albendazole
  • mebendazole
  • triclabendazole

All three belong to a class known as benzimidazole anthelmintics. They bind to beta-tubulin and pevent the elongation of microtubules.

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20
Q

Is the bioavailability of benzimidazole anthelmintics (e.g. albendazole) low, or high?

A

Low (about 5%)

Albendazole is prefererd for systemic infections (e.g. cysticercosis). To help with absorption, it is usually taken with a high-fat meal.

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21
Q

For treating systemic worm infections, albendazole is administered for days-weeks. Name two organs this drug is toxic to.

A

Liver - hepatotoxicity (increased AST, ALT)

Bone marrow - myelosuppression

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22
Q

Which is a more active anthelmintic agent: albendazole or it’s primnary metabolite, albendazole sulfoxide?

A

albendazole sulfoxide is more active than the “parent drug”

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23
Q

What type of active metabolite does nitazoxanide form in worms?

A

a hydroxylamine (this is the active form of the drug that inhibits PFOR)

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24
Q

What anthelmintic drug inhibits the enzyme, pyruvate:ferredoxin oxidoreductase (PFOR), which results in ATP depletion?

A

nitazoxanide (actually, the hydroxylamine metabolite of nitazoxanide is the active, PFOR inhibitor)

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25
Q

What drug can be used to treat Fasciola (common liver fluke), Giardia, or Cryptosporidium, and works by inhibiting ATP synthesis?

A

nitazoxanide

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26
Q

What type of ion do invertebrate (worm and insect) Glutamate channels conduct?

A

Chloride (Cl-)

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27
Q

How does ivermectin work?

A

Increases Cl- conductance through invertebrate (worm and insect) glutamate channels. This causes hyperpolarization and inhibits transmission of neuronal signals. Leads to paralysis and death.

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28
Q

What is the Mazzotti reaction?

A

A post-treatment reaction in treating systemic worm infections (e.g. filariasis). Dying worms in the body cause an immune reaction, including fever, edema, itching, and possible anaphylaxis.

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29
Q

Praziquantel has several effects. It partly works by increasing the conduction of what ion across worm cell membranes?

A

Calcium

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30
Q

What organelle in worm cells does niclosamide inhibit?

A

mitochondria

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31
Q

What anthelmintic drug is mainly used for beef or fish tapeworm, and works by ‘uncoupling’ the electron transport chain?

A

niclosamide

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32
Q

Name two pediculosidal drugs that kill lice eggs.

A
  • spinosad
  • malathion
    note: malathion’s activity against eggs can be unreliable. Also, resistance to the drug is increasing in many areas.
33
Q

Are there any OTC products available that kill adult lice and their eggs?

A

No, malathion and spinosad are the ones that kill eggs, and are prescription-only drugs.

34
Q

What is the pediculocidal mechanism for benzyl alcohol?

A

Clogs respiratory spiracles on lice (chokes them)

35
Q

What is the pediculocidal mechanism for spinosad?

A

GABA antagonist.

Since GABA is an inhibitory neurotransmitter, antagonism of GABA receptors by spinosad causes the opposite effect (excitation, leading to involuntary spasms and death)

36
Q

What is the natural source of pyrethrins and permithrin?

A

flowers (chrysanthemum)

37
Q

What P450 enzyme inhibitor is commonly added as a synergist, with pyrethrins and permethrin?

A

piperonyl butoxide - blocks metabolism in the insect, so they cannot ‘detoxify’ pyrethrins and permethrin.

38
Q

What is the active metabolite of malathion?

A

malaoxon

Insects convert malathion into malaoxon. Humans are not very good at doing this (we usually detoxify it by carboxylesterases)

39
Q

What is the target of malaoxon (the active metabolite of malathion)?

A

Acetylcholinesterase (AChE)

Blocking AChE leads to accumulation of acetylcholine (ACh), and “cholinergic toxicity”

40
Q

How does crotamiton kill scabies?

A

Mechanism is unknown

41
Q

How does crotamiton stop itching?

A

Blocks TRPV4 calcium channels in the skin (on sensory nerve endings).

42
Q

Name two drugs of choice for treating crytosporidium

A
  • paromomycin
  • nitazoxanide

Cryto is typically self-resolving in 1-2 weeks. However, it is treated with drugs in immunocompromized patients.

43
Q

What are the clinical uses of metronidazole and tinidazole?

A
  • Entamoeba histolytica (amebiasis)
  • Giardia lamblia
  • Trichomonas vaginalis

Brand name of metronidazole = Flagyl

44
Q

What is pyrimethamine used for?

A

Toxoplasma gondii (toxoplasmosis)

It is also used for Isospora belii (aka. cystoisosporiasis), an intestinal parasite that affects immunocompromised hosts.

(note, we did not cover Isospora in lecture, you will not be expected to know this for the exam)

45
Q

What drug class does paromomycin belong to?

A

Aminoglycosides

46
Q

What is the mechanism for paromomycin?

A

Protein synthesis inhibitor (30S subunit)

47
Q

Is paromomycin absorbed from the GI tract?

A

No, because it is an aminoglycoside. That is OK - it is a luminal drug for GI parasites.

48
Q

What type of parasite is iodoquinil used for?

A

Amoebas (e.g. Entamoeba histolyticum)

49
Q

What is the mechanism for iodoquinil?

A

Not fully known. It binds metals, and may be a metal (e.g. Fe2+, Cu2+) ionophore.

50
Q

Iodoquinil is anti-protozoal. What else does it kill?

A

Bacteria and fungi. It is used topically for dermatoses.

51
Q

What is the mechanism for metronidazole, and tinidazole?

A

Generates reactive compounds and ROS that cause:

  • DNA damage
  • Protein damage
  • Glutathione (GSH) depletion
52
Q

Patients should avoid drinking alcohol while taking metronidazole or tinidzaole. What happens if they do?

A

Disulfiram-like reaction: flushing, headache, nausea, tachycardia, dyspnea. It is caused by the off-target inhibition of aldehyde dehydrogenase by the drug. The buildup of acetaldehyde after consuming alcohol causes the symptoms.

53
Q

Metronidazole kills Entamoeba, Giardia, and Trichomonas. What type of bacteria does metronidazole kill?

A

Anaerobes.

Metronidazole is one of few antibiotics that kills both B. fragilis and C. difficile. It is also used (along with other drugs) for H. pylori. Also, it has some mild anti-inflammatory effects. A versitile drug!

54
Q

What enzyme does pyrimethamine inhibit?

A

Dihydrofolate reductase (DHFR)

It is usually given with sulfadiazine (DHPS inhibitor).

Pyrimethamine (Daraprim) is VERY expensive right now. TMP-SMX is an alternative (this drug combniation inhibits the same pathway, but is less effective against parasites vs. bacteria)

55
Q

What bone marrow protectant drug is usually given with pyrimethamine?

A

leucovorin

56
Q

Name a drug of choice for Chagas disease (American tropanosomiasis).

A

Benznidazole

57
Q

Pentamidine is a drug of choice for West African tropanosomiasis. What else is it used for (in AIDS patients)?

A

Prophylaxis or treatment of PCP penumonia.

58
Q

What “sign” is oberved in African tropanosomiasis (T. brucei)?

A

Winterbottom’s sign

59
Q

What “sign” is oberved in Chagas disease (American tropanosomiasis, T. cruzi)?

A

Romana’s sign

60
Q

What is the mechanism for benznidazole (used in Chagas disease)?

A

Forms a reactive product that causes

  • DNA damage
  • Protein damage
  • Glutathione (GSH) depletion

very similar to metronidazole, tinidazole!

61
Q

What drug used for Chagas disease can be toxic to skin (e.g. causing TEN or erythema multiforme)?

A

Benznidazole

62
Q

What cell type is infected by Leishmania?

A

Macrophages

63
Q

What is the mechanism for chloroquine?

A
  • hemozoin inhibitor (main mechanism)
    also: raises vacuole pH, and inhibits DNA and RNA polymerases
64
Q

What is the mechanism for primaquine?

A

ROS generation, damages parasite

65
Q

What are the main mechanisms for artemether and lumefantrine (taken together as CoArtem)?

A

artemether - generates free radicals, damages parasite

lumefantrine - hemozoin inhibitor

66
Q

Artemether belongs to a drug class called artemisinin derivatives. What is the common name for the plant these come from?

A

Annual Wormwood (aka sweet wormwood)

scientific name: Artemisia annua

A related drug that is an artemisinin derivative is artesunate (given IV for severe, life-threatening malaria)

67
Q

Is tafenoquine used for prophylaxis, or malaria treatment?

A

Either. It can be used for the prophylaxis of all malaria species, or for the treatment of Plasmodium vivax.

68
Q

Name two anti-malaria drugs that you should NOT use in patients with G6PDH deficiency?

A
  • primaquine
  • tafenoquine

Why? Because both of these drugs generate reactive oxygen species. Patients with G6PDH deficiency have red blood cells that are damaged by drugs that make ROS.

69
Q

What is the mechanism for atovaquone-proguanil (Maralone)?

A
  • atovaquone - disrupts electron transport chain in mitochondria
  • proguanil - prodrug to cycloguanil, a DHFR inhibitor
70
Q

What two antimalarial drugs are effective against the liver stage of the disease?

A
  • primaquine
  • tafenoquine
71
Q

Which antimalarial drugis effective against all three forms of the disease (liver, erythrocyte, gamete)?

A

tafenoquine

72
Q

What is the volume of distribution for chloroquine, large or small?

A

VERY large - this drug is often used as an example (and exam question) for drugs that have large volumes of distribution.

73
Q

What effect does chloroquine have on cardiac conduction?

A

Prolongs the QT interval. This can result in life-threatening arrhythmias (important to monitor EKG in at-risk patients)

74
Q

Which antimalarial drug has a very fast onset of action?

A

Artemether (and other artemisinin-derivatives, e.g. artesunate). That is the reason that they (especially artesunate) are used for serious (complicated) malaria, where you need to have quick action against the parasite.

75
Q

Atovaquone is one of the ingredients in Maralone (along with proguanil). Besides malaria, what other use does atovaquone have?

A

PCP pneumonia

76
Q

What is one of the most common adverse effects of chloroquine?

A

Itch (pruritis)

77
Q

Why does chloroquine accumulate in parasite (malaria) vacuoles?

A

Because it is ion-trapped. Chloroquine is basic. The vacuole is acidic. Therefore, chloroquine becomes charged in the vacuole and gets ‘trapped’ there.

78
Q

what is a luminal drug

A

a drug that is only effective against intestinal parasites

5200: Structural Integrity (19 decks)

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