Microbiology pharm – HY mixed antimicrobials III

a)

Inhibits Plasmodium heme polymerase.

b)

Tx for malaria (caused by the protozoan Plasmodium spp. transmitted by the Anopheles mosquito).

Malaria presents as hemolytic anemia, hepatosplenomegaly, waxing/waning fever patterns, and cerebral malaria (encephalopathy; P. falciparum).

USMLE answer = “resistance to chloroquine”; the wrong answer is “noncompliance with medication.”

Primaquine is used for P. vivax and ovale to kill hypnazoites (hepatic latent form of organism).

USMLE wants: “presence of extra-erythrocytic form of organism,” which refers to hypnazoites.

USMLE wants: “primaquine kills hypnazoites.”

Malaria: atovaquone + proguanil is well-known regimen.

African sleeping sickness: use sodium stibogluconate or liposomal amphotericin B (yes, even though the latter is antifungal).

Babesia: use atovaquone + azithromycin.

Chagas disease: use nifurtimox.

23F + went to Africa + came back with hemolytic disease; Dx? –> answer = malaria.

23F + lives in Pennsylvania + tick bite + hemolytic disease; Dx? –> answer = Babesia.

Babesia –> (malaria-like hemolytic disease but limited to the USA).

46M + lives in Connecticut + tick bite + hemolytic disease; Dx? –> answer = Babesia.

46M + went to Africa + came back with hemolytic disease; Dx? –> answer = malaria.

Babesia –> (malaria-like hemolytic disease but limited to the USA).

a)

MOA of permethrin?

• Inhibits sodium channel inactivation –> depolarization + cell death.

b)

When is permethrin the answer?

• Topical permethrin used for scabies and lice.
• 44M + lived in homeless shelter for 4 months + has itchy hands + photo shows you red dots on hands + Q says topical antifungals were not effective; Tx? –> answer = permethrin.
  • “Linear burrows” are classic descriptor for scabies infection, but exam images you get won’t really resemble this.
• 9F + head lice; Tx? –> answer = permethrin.

Tx for leishmaniasis (caused by the protozoan Leishmania donovani transmitted by Phlebotomus sandfly).

Antimony compound.

Cutaneous leishmaniasis: most common; presents as ulcer on the arm.

Visceral leishmaniasis (kala azar): starts as cutaneous, then progresses to hepatosplenomegaly + pancytopenia.

Liposomal amphotericin B (antifungal) is another Tx for leishmaniasis.

Tx for Chagas disease (caused by the protozoan Trypanosoma cruzi transmitted by reduviid bug [“kissing bug”]).

Acute Chagas disease: swollen nodule at site of bite (called Romana’s sign if on the eyelid; chagoma if elsewhere).

Chronic Chagas disease (untreated): dilated cardiomyopathy, secondary achalasia, megaureter, toxic megacolon.

Tx for African trypanosomiasis (aka African sleeping sickness, caused by protozoan Trypanasoma brucei transmitted by the Tsetse fly).

Insomnia at night + somnolence during the day; fevers.

a)

Inhibits dihydrofolate reductase (same as trimethoprim and methotrexate, albeit these drugs all have very different uses).

b)

Tx for toxoplasmosis = sulfadiazine + pyrimethamine.

In contrast, prophylaxis for toxo (AIDS with CD4 count <100) = trimethoprim/sulfamethoxazole (TMP/SMX). Patients are usually incidentally covered for toxo prophylaxis because TMP/SMX is commenced for Pneumocystis jirovecii prophylaxis at CD4 count <200.

If cat / cat feces not listed as an answer, choose consumed pork. 

35F + pregnant + has toxo + Q asks how she got it; cat not listed as an answer; student says “Wtf? I thought it was cats.” –> answer = pork.

• Inhibit microtubules.
  • USMLE also wants you to know the drugs that relate to microtubules:
    • Prevent assembly/formation of microtubules: 
      • Vinblastine
      • Vincristine
      • Colchicine
      • -Bendazoles (i.e., mebendazole, albendazole), which are anti-helminthic agents; do not confuse with -azoles.
      • Griseofulvin
    • Hyper-stabilize microtubules / prevent microtubule disassembly:
      • Taxanes (i.e., paclitaxel, docetaxel) –> odd one out, because the others all inhibit assembly/formation of microtubules, whereas taxanes hyper-stabilize / prevent disassembly.

Tx for many helminth infections, notably the nematodes (roundworms), such as Ascaris lumbricoides, Enterobius vermicularis.

Tx for many nematode infections.

Think of this as akin to mebendazole –> “Oh ok. Weird drug. But all I need to know is: if I see it, it’s basically just the same as mebendazole.”

Tx for various cestode and trematode (fluke) infections.

• • HY cestode Tx: cysticercosis (in contrast, neurocysticerosis is albendazole).
  • HY trematode Tx: schistosomiasis.

Tx for Filarial infections (nematode infections transmitted by insects).

Notable use: Wuchereria bancrofti (elephantiasis).

Tx for onchocerciasis (nematode infection caused by Onchocerca volvulus [river blindness]), tranmitted by the black fly).

Can be given orally to treat scabies (normally Tx for scabies is topical permethrin).

Dx = Schistosoma hematobium –> lays eggs in bladder wall and vesicular veins (drain the bladder) that can calcify; granulomatous disease.

Tx is with praziquantel. Schistosoma is a trematode (fluke).

Dx = onchocerciasis (Onchocerca volvulus, a nematode [roundworm]) –> river blindness –> black fly, black bite/lesion, black eyesight (blindness).

Tx = ivermectin.

Diethylcarbamazine is used for Filariasis (nematode infections caused by bites), but for onchocerciasis, ivermectin is the HY USMLE Tx. Diethylcarbamazine  is notably Wuchereria bancrofti (elephantiasis).

Chagas disease (caused by the protozoan Trypanosoma cruzi transmitted by reduviid bug [“kissing bug”]).

Acute Chagas disease: swollen nodule at site of bite (called Romana’s sign if on the eyelid; chagoma if elsewhere).

Chronic Chagas disease (untreated): dilated cardiomyopathy, secondary achalasia, megaureter, toxic megacolon.

Sodium stibogluconate

• Tx for leishmaniasis (caused by the protozoan Leishmania donovani transmitted by Phlebotomus sandfly).
• Antimony compound.
• Cutaneous leishmaniasis: most common; presents as ulcer on the arm.
• Visceral leishmaniasis (kala azar): starts as cutaneous, then progresses to hepatosplenomegaly + pancytopenia.
• Liposomal amphotericin B (antifungal) is another Tx for leishmaniasis.