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Pharmacology > Deja Ch 2.2 Antiviral > Flashcards

Deja Ch 2.2 Antiviral Flashcards

1
Q

What enzyme adds the first phosphate to acyclovir?

A

Viral thymidine kinase

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2
Q

True or False? Monophosphorylated acyclovir is converted to the triphosphate form by viral enzymes.

A

False (host cell kinases are responsible for these reactions)

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3
Q

How does acyclovir triphosphate work as an antiviral agent?

A

Inhibits viral DNA replication by competing with deoxyguanosine triphosphate for viral DNA polymerase; incorporated into the viral DNA molecule and acts as a chain terminator

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4
Q

How does acyclovir triphosphate work as a chain terminator?

A

Lacks the ribosyl 3’ hydroxyl group

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5
Q

How do viruses become resistant to acyclovir?

A

Downregulation of viral thymidine kinase; lacking thymidine kinase altogether; altered specificity of viral thymidine kinase; altered specificity of viral DNA polymerase

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6
Q

Acyclovir is effective in treating which virus types?

A

Herpes simplex virus (HSV) 1 and 2; varicella-zoster virus (VZV). Acyclovir is 10 _ more potent against HSV than VZV

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7
Q

Is acyclovir effective in treating postherpetic neuralgia?

A

No (only effective against acute neuritis)

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8
Q

What is the oral bioavailability of acyclovir?

A

15%-30%. There is minimal systemic distribution after topical application.

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9
Q

What is the half-life of acyclovir in adults?

A

2.5-3 hours

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10
Q

Why is it necessary to maintain adequate hydration in patients receiving IV acyclovir therapy?

A

To prevent crystalluria or interstitial nephritis. Slow infusion additionally helps to avoid these adverse reactions.

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11
Q

What is the name of the prodrug that is converted to acyclovir and L-valine by first-pass metabolism?

A

Valacyclovir

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12
Q

What is the advantage of valacyclovir over acyclovir?

A

Higher oral bioavailability of 54%-70%

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13
Q

Famciclovir is a prodrug that is metabolized to what active metabolite?

A

Penciclovir

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14
Q

What is the bioavailability of penciclovir after oral administration of famciclovir?

A

70%

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15
Q

Is famciclovir effective in viral strains resistant to acyclovir secondary to mutated DNA polymerase?

A

Yes

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16
Q

Is famciclovir effective in viral strains resistant to acyclovir secondary to lack of thymidine kinase?

A

No

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17
Q

What is the mechanism of action of ganciclovir?

A

Phosphorylated to a substrate which competitively inhibits binding of deoxyguanosine triphosphate to DNA polymerase, thereby inhibiting viral DNA synthesis

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18
Q

Does ganciclovir have chain-terminating ability?

A

No

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19
Q

Ganciclovir is effective in treating which virus types?

A

HSV; VZV; human herpes virus (HHV)-6 and 8; cytomegalovirus (CMV). Activity against CMV is 100 _ greater than acyclovir. It may be used intraocularly for CMV retinitis.

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20
Q

What is the advantage of valganciclovir over its parent drug ganciclovir?

A

Valganciclovir (the valine ester) has up to 60% better oral availability than ganciclovir.

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21
Q

What is ganciclovir’s dose-limiting adverse effect?

A

Myelosuppression; thrombocytopenia; anemia; leukopenia

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22
Q

What are the adverse effects of ganciclovir?

A

Crystalluria; mucositis; rash; fever; hepatotoxicity; seizures; diarrhea; nausea; hematotoxicity

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23
Q

What is cidofovir used for?

A

CMV retinitis most commonly. It also has activity against HSV-1 and 2, varicella zoster virus (VZV), Epstein-Barr virus (EBV), HHV-6 and 8, adenovirus, poxviruses, polyomaviruses, and human papilloma virus (HPV).

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24
Q

What antiviral agent is a pyrophosphate analogue that acts as an inhibitor of viral RNA and DNA polymerase and HIV reverse transcriptase?

A

Foscarnet

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25
Q

Does foscarnet require activation by thymidine kinase?

A

No

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26
Q

Foscarnet is effective in treating which virus types?

A

Acyclovir-resistant HSV and VZV; ganciclovir-resistant CMV

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27
Q

Does foscarnet cause hematotoxicity?

A

Yes

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28
Q

What are the major adverse effects of foscarnet?

A

Hematotoxicity; fever; seizures; electrolyte abnormalities; nausea; vomiting; diarrhea

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29
Q

What types of electrolyte abnormalities can foscarnet cause?

A

Hyper- or hypocalcemia; hyper- or hypomagnesemia; hyper- or hypophosphatemia; hypokalemia

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30
Q

True of False? Amantadine is effective in treating both influenza A and B.

A

False (it is effective against the influenza A virus only)

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31
Q

What is the antiviral mechanism of action of amantadine?

A

Blocks the uncoating of influenza A virus, thereby preventing penetration of the virus into host cells

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32
Q

What other noninfectious disease processes is amantadine used for?

A

Parkinson disease; drug-induced extrapyramidal symptoms. It also increases dopamine levels in the synaptic cleft by either inhibiting reuptake into presynaptic neurons or by increasing release from presynaptic neurons. It may have anticholinergic effects.

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33
Q

What are the adverse effects of amantadine?

A

Seizures; insomnia; nervousness; livedo reticularis; orthostatic hypotension; peripheral edema; dry nose; xerostomia; nausea; anorexia

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34
Q

What is livedo reticularis?

A

A purplish discoloration of the skin caused by dilation of capillaries and venules secondary to stasis or changes in underlying blood vessels

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35
Q

Name two drugs that inhibit neuraminidase of both influenza A and B, thereby decreasing the likelihood of viral penetration into host cells:

A

Oseltamivir; zanamivir

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36
Q

Which neuraminidase inhibitor has an oral inhalational route of administration?

A

Zanamivir

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37
Q

Ribavirin is effective in treating which virus types?

A

Respiratory syncytial virus (RSV); influenza A and B; hepatitis C virus (HCV)

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38
Q

Ribavirin is used in conjunction with what other drug to treat HCV?

A

Interferon-alpha (IFN-_)

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39
Q

What are the adverse effects of ribavirin?

A

Anemia; neutropenia; thrombocytopenia; anorexia; headache; conjunctivitis; nausea; pharyngitis; lacrimation; alopecia; rash; flu-like syndrome; teratogenicity (pregnancy category X)

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40
Q

Name the major adverse effects of IFN-_:

A

Flu-like symptoms; depression; alopecia; insomnia; nausea

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41
Q

What is the name of the only available nucleotide reverse transcriptase inhibitor?

A

Tenofovir

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42
Q

Give examples of nucleoside reverse transcriptase inhibitors (NRTIs):

A

Zidovudine (AZT); stavudine (d4T); lamivudine (3TC); didanosine (ddl); abacavir (ABC); emtricitabine (FTC)

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43
Q

What adverse effect(s) are associated with all NRTIs?

A

Lactic acidosis with hepatic steatosis

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44
Q

What is the general mechanism of action of NRTIs?

A

Interference with HIV viral RNA-dependent DNA polymerase resulting in inhibition of HIV viral replication

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45
Q

What two NRTIs are thymidine analogs?

A

Zidovudine; stavudine

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46
Q

What NRTI is an adenosine analog?

A

Didanosine

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47
Q

What NRTI is a guanosine analog?

A

Abacavir

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48
Q

What two NRTIs are cytosine analogs?

A
  1. Emtricitabine 2. Lamivudine
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49
Q

Which NRTI should not be rechallenged if hypersensitivity is expected?

A

Abacavir (symptoms include fever, rash, nausea, vomiting, malaise, fatigue, and respiratory dysfunction)

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50
Q

Which NRTI can cause hyperuricemia?

A

Didanosine

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51
Q

Which two NRTIs can cause pancreatitis?

A
  1. Didanosine 2. Stavudine (dose-limiting effect)
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52
Q

Which two NRTIs can cause peripheral neuropathy?

A
  1. Didanosine 2. Stavudine (dose-limiting effect)
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53
Q

What is didanosine’s dose-limiting adverse effect?

A

Pancreatitis

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54
Q

What is stavudine’s dose-limiting adverse effect?

A

Peripheral neuropathy

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55
Q

What are the main adverse effects of AZT?

A

Anemia and neutropenia (dose-limiting effect/potentiated by vitamin B12); headache; nausea; insomnia; body aches; lactic acidosis

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56
Q

What is the dose-limiting adverse effect of AZT?

A

Hematotoxicity

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57
Q

What antiretroviral agent can cause Fanconi syndrome?

A

Tenofovir. Fanconi syndrome is impairment of the proximal tubule resulting in increased phosphate and calcium losses.

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58
Q

What NRTI can cause altered LFTs, lipoatrophy, hyperlipidemia, and ascending paresis?

A

Stavudine

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59
Q

Name three nonnucleoside reverse transcriptase inhibitors (NNRTIs):

A
  1. Delavirdine 2. Efavirenz 3. Nevirapine
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60
Q

What is the mechanism of action of efavirenz?

A

Binds directly to reverse transcriptase and blocks the RNA-and DNA-dependent DNA polymerase activity of reverse transcriptase

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61
Q

What is the class adverse effect(s) of the NNRTIs?

A

Rash

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62
Q

Which NNRTI can cause hepatitis and hepatic necrosis?

A

Nevirapine

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63
Q

Which NNRTI can cause abnormal dreams, impaired concentration, dizziness, and altered LFTs?

A

Efavirenz

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64
Q

Which NNRT can produce a false-positive urine test for Cannabis?

A

Efavirenz (in about 50% of patients)

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65
Q

Do NNRTIs require metabolic activation?

66
Q

Do NRTIs require metabolic activation?

67
Q

What is the name of the drug that inhibits fusion of the HIV-1 virus with CD4 cells by binding to and blocking the conformational change in gp41 required for membrane fusion and entry into CD4 cells?

A

Enfuvirtide (fusion inhibitor)

68
Q

What are the adverse effects of enfuvirtide?

A

Pain, induration, erythema, and nodules at the injection site; nausea; vomiting; diarrhea; fatigue

69
Q

Give examples of protease inhibitors:

A

Atazanavir; indinavir; lopinavir; fosamprenavir; nelfinavir; ritonavir; saquinavir; tipranavir; amprenavir; darunavir

70
Q

What adverse effect(s) are associated with the protease inhibitors?

A

Hepatotoxicity; fat maldistribution; insulin resistance; osteonecrosis; increased bleeding in hemophiliac patients

71
Q

Are protease inhibitors metabolized by P-450 enzymes?

72
Q

Do protease inhibitors inhibit or induce P-450 enzymes?

A

They inhibit P-450 enzymes.

73
Q

What is HIV protease responsible for?

A

Cleaves the Gag-Pol polyprotein of HIV (the gag region of the gene codes for structural proteins whereas the Pol region of the gene codes for protease, reverse transcriptase, and integrase)

74
Q

The combination of atazanavir and indinavir can cause what possible adverse effect?

A

Hyperbilirubinemia

75
Q

Patients with sulfonamide allergy should use caution when taking which two protease inhibitors?

A
  1. Tipranavir 2. Fosamprenavir
76
Q

Which protease inhibitor can cause an altered taste sensation?

77
Q

Which two protease inhibitors can cause asthenia (lack of strength)?

A
  1. Lopinavir 2. Ritonavir
78
Q

Which protease inhibitor can cause kidney stone formation?

79
Q

Which protease inhibitor can cause numbness around the mouth?

80
Q

What type of prophylaxis is given to a person stuck with a potentially HIV contaminated needle?

A

Zidovudine and lamivudine for 1 month (protease inhibitor should be added for high-risk exposures)

81
Q

How is maternal-fetal HIV transmission prevented in mothers?

A

Zidovudine beginning at 14-34 weeks’ gestation and continued until start of labor; during labor and delivery, zidovudine until the umbilical cord is clamped

82
Q

How is maternal-fetal HIV transmission prevented in neonates?

A

Zidovudine started 8-12 hours after birth and continued for 6 weeks

83
Q

Amebiasis is generally treated with what drug combination?

A

Metronidazole and diloxanide

84
Q

What is the mechanism of action of metronidazole?

A

Mixed amebicide (effective against both luminal and systemic forms of disease); nitro group of metronidazole acts as an electron acceptor, thereby forming reduced cytotoxic compounds that lead to inhibition of protein synthesis and DNA strand breakage

85
Q

What are the adverse effects of metronidazole?

A

Nausea; vomiting; metallic taste sensation; disulfiram-like reaction

86
Q

Give examples of medications that can cause a disulfiram-like reaction:

A

Metronidazole; chlorpropamide; cefotetan; cefamandole; cefoperazone

87
Q

What is the antimicrobial spectrum of metronidazole?

A

Entamoeba histolytica; Giardia lamblia; Trichomonas vaginalis; bacterial anaerobes; C. difficile

88
Q

Metronidazole is contraindicated in which trimester of pregnancy?

A

First trimester during organogenesis since teratogenicity has not been effectively ruled out

89
Q

Can metronidazole cross the blood-brain barrier (BBB)?

90
Q

What is the mechanism of action of diloxanide?

A

Luminal amebicide (effective against luminal forms of disease) used in the treatment of asymptomatic amoebic cyst passers

91
Q

What are the adverse effects of diloxanide?

A

Contraindicated in pregnancy and children less than 2 years old; dry mouth; pruritus; flatulence

92
Q

What are the four species of Plasmodium

A
  1. Malariae 2. Falciparum 3. Vivax 4. Ovale
93
Q

What is the most dangerous/life-threatening Plasmodium species?

A

Falciparum

94
Q

What are the three stages of the malarial parasite life cycle primarily targeted by antimalarial drugs?

A
  1. Erythrocytic stage 2. Exoerythrocytic stage 3. Gametocytic stage
95
Q

What is the oldest antimalarial drug still in use?

A

Quinine (“Jesuit Bark”)

96
Q

Quinine has been replaced by which antimalarial drug?

A

Chloroquine (more potent and less toxic than quinine)

97
Q

What drugs are effective against the exoerythrocytic forms of malaria?

A

Primaquine; atovaquone + proguanil (Malarone)

98
Q

What drug is effective against the gametocytic (hepatic) forms of malaria?

A

Primaquine

99
Q

Is primaquine effective against erythrocytic forms of malaria?

100
Q

Give examples of antimalarial drugs that are effective against the erythrocytic forms of malaria:

A

Hydroxychloroquine; chloroquine; mefloquine; pyrimethamine; quinine; atovaquone + proguanil; artemisinin

101
Q

What drug is effective against relapsing forms of P. vivax and P. ovale malarias?

A

Primaquine. To prevent recurrence of infection, hepatic forms of these parasites must be eliminated.

102
Q

What are the adverse effects of primaquine?

A

Hemolytic anemia in patients with G6PD deficiency; methemoglobinemia; agranulocytosis

103
Q

What is the drug of choice for acute attacks of malaria caused by chloroquine-sensitive strains of P. falciparum and P. vivax?

A

Chloroquine

104
Q

Does chloroquine have a large or small Vd?

105
Q

What is the mechanism of action of chloroquine?

A

It concentrates within parasite food vacuoles and raises pH leading to inhibition of growth; inhibits hemoglobin metabolism and utilization by parasites; concentrates within parasite vacuoles and raises pH leading to inhibition of growth; binds to ferriprotoporphyrin IX leading to membrane damage; inhibits DNA and RNA polymerase

106
Q

What continents contain the largest repositories of chloroquine-resistant P. falciparuml

A

Africa, Asia

107
Q

What are the adverse effects of chloroquine?

A

ECG changes (quinidine-like effects); headaches; pruritus; mucosal pigmentary changes (blue-black); photosensitivity; nausea; vomiting; diarrhea; aplastic anemia; agranulocytosis; neutropenia; thrombocytopenia; retinopathy; tinnitus; reduced hearing

108
Q

Chloroquine is contraindicated in patients with what disease states?

A

Porphyria; psoriasis

109
Q

What are the major adverse effects of quinine?

A

Cinchonism (nausea, vomiting, diarrhea, tinnitus, vertigo); hemolytic anemia; digoxin toxicity

110
Q

What other medication can cause cinchonism?

111
Q

Is quinine acidic or basic?

112
Q

How can the urinary excretion of quinine (or chloroquine) be enhanced?

A

Acidification of the urine

113
Q

Name two newer antimalarials that are chemically related to quinine:

A
  1. Halofantrine 2. Lumefantrine
114
Q

What can be used to acidify the urine?

A

Ammonium chloride

115
Q

What is the mechanism of action of pyrimethamine?

A

Inhibits nucleic acid and protein metabolism in the parasites; plasmodial dihydrofolate reductase (DHFR) inhibitor

116
Q

The antimalarial effects of pyrimethamine can be potentiated by combining it with which drugs?

A

Sulfonamides (synergistic blockade of folic acid synthesis).

117
Q

How is folate-deficient megaloblastic anemia reversed in patients taking pyrimethamine?

A

Leucovorin

118
Q

What is the mechanism of action of leucovorin?

A

As a reduced form of folic acid, leucovorin supplies human cells with the necessary cofactor blocked by DHFR inhibitors.

119
Q

What kind of compounds are the antimalarial drug artemisinin and its derivatives?

A

Sesquiterpene lactones (the active ingredient in a 2000-year-old Chinese herb—Qing Hao).

120
Q

What is the antimalarial mechanism of action of artemisinin?

A

It is thought that it is activated by heme to irreversibly decompose generating free radicals that form adducts mostly with proteins and lipids.

121
Q

Give examples of antimalarial drugs used in artemisinin combination therapies (ACT):

A

Pyrimethamine/sulfadoxine (Fansidar), mefloquine, amodiaquine

122
Q

What is the name of the most promising antimalarial vaccine?

A

RTS-S/AS02A or Mosquirix

123
Q

Which genetic diseases/conditions may help protect against malarial infections?

A

Sickle cell trait; G6PD deficiency

124
Q

Trypanosoma cruzi is responsible for causing what disease?

A

American trypanosomiasis (Chagas disease)

125
Q

T. brucei gambiense and T. brucei rhodesiense are responsible for causing what disease?

A

African trypanosomiasis (sleeping sickness)

126
Q

What drug is used as a suppressive agent in patients with acute T. cruzi infections?

A

Nifurtimox

127
Q

What is the mechanism of action of nifurtimox?

A

Forms intracellular oxygen-free radicals which are toxic to the parasite because of its lack of catalase (oxygen radical scavenger)

128
Q

What drug is used to treat African sleeping sickness with CNS involvement?

A

Eflornithine for West African trypanosomiasis; melarsoprol for East African trypanosomiasis

129
Q

What are the adverse events of melarsoprol?

A

Hypersensitivity; abdominal pain; vomiting; hemolytic anemia in patients with G6PD deficiency; encephalopathy

130
Q

What two drugs are used in the early stages of African sleeping sickness?

A
  1. Pentamidine (first choice for West African sleeping sickness) 2. Suramin (first choice for East African sleeping sickness)
131
Q

Does pentamidine cross the BBB?

A

No. Therefore it cannot be used for late trypanosomiasis with CNS involvement.

132
Q

What are the two routes of administration of pentamidine?

A
  1. IV 2. Aerosol
133
Q

What fungus is pentamidine commonly used to treat?

A

Pneumocystis carinii

134
Q

What drug combination is used for prophylaxis against P. carinii?

A

Trimethoprim-sulfamethoxazole

135
Q

What is the treatment of choice for T. gondii?

A

Pyrimethamine + sulfadiazine

136
Q

How do humans become infected with T. gondii?

A

Ingestion of undercooked, infected meat; contact with infected cats

137
Q

Can pregnant mothers transmit T. gondii to the fetus?

A

Yes (remember TORCH syndromes)

138
Q

What are the three types of leishmaniasis infections?

A
  1. Visceral 2. Cutaneous 3. Mucocutaneous
139
Q

What is the drug of choice for treating leishmaniasis?

A

Stibogluconate (pentavalent antimony compound)

140
Q

What is another name for the nematodes?

A

Roundworms

141
Q

What is another name for the trematodes?

142
Q

What is another name for the cestodes?

143
Q

What drug is commonly used to treat trematode infections?

A

Praziquantel

144
Q

What is the mechanism of action of praziquantel?

A

Increases cell permeability to calcium, thereby increasing contractions with subsequent paralysis of musculature

145
Q

What is the mechanism of action of mebendazole?

A

It irreversibly blocks glucose uptake; inhibits microtubule polymerization

146
Q

What are the adverse effects of mebendazole?

A

Diarrhea; abdominal pain; contraindicated during pregnancy

147
Q

What is the mechanism of action of albendazole?

A

It interferes with microtubule polymerization; inhibits adenosine triphosphate (ATP) production thereby depleting energy availability

148
Q

What is the mechanism of action of thiabendazole?

A

Inhibits helminth-specific mitochondrial fumarate reductase

149
Q

What types of cutaneous adverse effects are caused by thiabendazole?

A

Stevens-Johnson syndrome; erythema multiforme

150
Q

What is the mechanism of action of pyrantel?

A

Depolarizing neuromuscular blocker thereby causing paralysis of musculature

151
Q

What types of helminths are affected by praziquantel?

A

Trematodes; cestodes

152
Q

What types of helminths are affected by mebendazole?

153
Q

What types of helminths are affected by pyrantel?

154
Q

What is the drug of choice for treating Enterobius vermicularis?

A

Mebendazole

155
Q

What is the common name for E. vermicularis?

156
Q

What is the drug of choice for treating Onchocerca volvulus (onchocerciasis or river blindness)?

A

Ivermectin

157
Q

What is the mechanism of action of ivermectin?

A

Acts at helminthic gamma-aminobutyric acid (GABA) receptors, thereby enhancing influx of chloride and causing hyperpolarization and paralysis

158
Q

Why does onchocerciasis potentially lead to blindness?

A

A bacteria (Wolbachia sp.) that colonizes many parasitic worms, including the nematode that causes onchocerciasis, is an important factor in the inflammatory response that leads to blindness.

159
Q

What is another name for onchocerciasis?

A

River blindness

160
Q

What drug is commonly used to treat cestode infections?

A

Niclosamide

161
Q

What is the mechanism of action of niclosamide?

A

Inhibits mitochondrial phosphorylation of ADP to ATP, thereby depleting energy availability

162
Q

Is niclosamide active against the ova of cestodes?

A

No; only active against cestode’s scolex and segments

Pharmacology (25 decks)

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