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PDA 3 > Gulsevin Exam 3 Materials > Flashcards

Gulsevin Exam 3 Materials Flashcards

1
Q

Malaria

How is malaria transmitted to humans?

A

mosquitoes

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2
Q

Malaria

What are the signs/symptoms of malaria?

A

overall, death of red blood cells= anemia
- chills
- fever
- sweating
- headache
- fatigue
- anorexia
- nausea
- vomiting
- diarrhea

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3
Q

Malaria

What are the 5 species of plasmodium that cause malaria in humans?

A
  • plasmodium falciparum
  • P. vivax (hypnozoite formation)
  • P. malariae
  • P. ovale (hypnozoite formation)
  • P. knowlesi

first 2 are the most common in the US

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4
Q

Malaria

What role does the gametocyte play in the life cycle of Plasmodium spp.?

A

gametocytes are specialized cells for transmission that allow plasmodium spp. to be transferred to the mosquito. gametocytes can be differentiated from merozoites.

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5
Q

Malaria

What role does the sporozoite play in the life cycle of Plasmodium spp.?

A

sporozoites come from oocyst in the mosquitos stomach and travel to the salivary glands to transmit plasmodium spp. via saliva to another human. once in the human host, sporozoites travel to the liver to replicate and lyse infected hepatocytes. merozoites are then released into the humans blood circulation.

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6
Q

Malaria

What role does the merozoites play in the life cycle of Plasmodium spp.?

A

merozoites are released in the bloodstream after sporozoites infect and lyse hepatocytes. merozoites infect erythrocytes- undergoing asexual cycles of erthrocytic infection and lysis. merozoites differentiate into gametocytes or P. vivax and P. ovale can also differentiate to dormant hypnozoites which remain in infected hepatocytes for months - years.

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7
Q

Malaria

What are the side effects of quinine’s used for the treatment of malaria?

A
  • CV= prolonged QT
  • CNS= fatigue, headache, disturbed sleep, nervousness, and ataxia
  • NM and skeletal= weakness and tremor
  • visual disturbances (rare)
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8
Q

Malaria

What is the mechanism of action of quinine’s for the treatment of malaria?

A

inhibition of heme polymerization, enhancement of oxidant production, and reaction with heme to form cytotoxic metabolites. disrupt the erythrocytic stage by interfering with parasitic hemoglobin metabolism and increasing intracellular pH.

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9
Q

Malaria

What drugs are 4-substituted quinoline derivatives?

A
  • chloroquine
  • hydroxychloroquine
  • mefloquine
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10
Q

Malaria

What is the drug of choice for malaria?

A

chloroquine

resistance is becoming common

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11
Q

Malaria

What 4-substituted quinoline derivatives may be used for prevention of malaria?

A

hydroxychloroquine and mefloquine

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12
Q

Malaria

What drugs are 8-aminoquinolines?

A
  • primaquine
  • tafenoquine
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13
Q

Malaria

What testing must be done to ensure safety when using 8-aminoquinolines for malaria?

A

glucose-6-phosphate dehydrogenase (G6PD) deficiency due to increased risk of damage to RBCs

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14
Q

Malaria

What is the spectrum of action of primaquine?

A

targets schizonticide and gametocytocide, and also hypnzoites of P. vivax and P. ovale

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15
Q

Malaria

What is the use of Tafenoquine?

A

activity against all stages of P. vivax and as prophylaxis

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16
Q

Malaria

What is the mechanism of action of 8-aminoquinolines?

A

creates reactive oxygen species (ROS) through metabolism of parent drug via CYP2D6

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17
Q

Malaria

What is the mechanism of action of atovaquone/proguanil?

A
  • atovaquone= interfers with pyrimidine synthesis
  • proguanil (prodrug)= inhibits dihydrofolate (DHF) reductase
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18
Q

Malaria

What is the WHO recommended treatment for malaria?

A

artemisinin and it’s derivatives in artemisinin-based combination therapy (ACT)

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19
Q

Malaria

What is the mechanism of action of artemisinin?

A

forms interactions with heme and proteins which are toxic to the cell which leads to cell death

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20
Q

Malaria

What drug is used to treat severe malaria?

A

artesunate

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21
Q

Malaria

What is the recommended dosage form by the CDC for artesunate?

A

IV

avaliable as IV, IM, PO, or rectum

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22
Q

Malaria

What is the mechanism of action of doxycycline?

A

binds 30S ribosomal subunit to block binding of tRNA to mRNA

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23
Q

Malaria

What is the use of doxycycline in malaria therapy?

A

prophylaxis for travelers in areas with chloroquine-resistant P. falciparum

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24
Q

Malaria

What is the dosing of Doxycycline for malaria prophylaxis?

A

100mg PO daily 1-2 days prior to travel, during travel and continue for 4 weeks after returning home

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25
Q

Malaria

Why can atovaquone/proguail be used for malaria prophylaxis?

A

acts at hepatic schizonts during initial infection

26
Q

Antivirals

What are the different mechanisms that prevent viral entry into host cell?

A
  • attachment inhibitors block the interactions between the host cell receptor (CD4) and viral glycoproteins
  • fusion inhibitors prevent the fusion of viral and host cell membranes
  • CCR5 receptors antagonists disrupt the interactions between the host cell receptors and viral glycoproteins
27
Q

Antivirals

When are viral entry inhibitors typically used?

A

HIV-1 infections

28
Q

Antiviral

What is the mechanism of action of attachment inhibitors?

A

bind gp120 protein (on the virus) to prevent the interaction with the host cells CD4 receptor= prevention of attachment

29
Q

Antiviral

What drugs are attachment inhibitors?

A

fostemsavir (prodrug) of temsavir (active compound)

30
Q

Antivirals

What is the indication of fostemavir?

A

HIV-1 in heavily treatment experienced adults with multidrug resistant HIV failing current antiviral regimens

31
Q

Antiviral

What is the use of ibalizumab?

A

monoclonal antibody for the treatment of HIV-1

32
Q

Antivirals

What is the mechanism of action of ibalizumab?

A

viral entry inhibitor, binds to host cells CD4 to prevent binding to gp120

33
Q

Antivirals

What is the dosing of ibalizumab?

A

long acting agent, injection every 2 weeks

34
Q

Antivirals

What is the mechanism of action of enfuvirtide?

A

viral fusion inhibitor, binds gp41 and mimics HIV-1 fusion machinery and prevents the fusion of viral and host cell membranes

35
Q

Antivirals

What is the indication of Enfuvirtide?

A

HIV

36
Q

Antivirals

What is the mechanism of action of maraviroc?

A

negative allosteric modulator of the T cell C-C chemokine receptor type 5 (CCR5) resulting in structural changes of CCR5 which leads to disruption of the interactions between CCR5 and gp120

37
Q

Antivirals

What is the use of neuraminidase inhibitors?

A

influenza A and B

38
Q

Antivirals

What is the mechanism of action of influenza neuraminidase inhibitors?

A

mimic the transition state of sialoside cleavage to bind influenza neuraminidase, to prevent the action of viral neuraminidase enzymes from cleaving the sialic acid moieties from cell glycoproteins

39
Q

Antivirals

What is the mechanism of action of integrase strand transfer inhibitors (INSTIs)?

A

bind to active site of the integrase enzyme forming a ternary complex (INSTI + integrase + 3’ processed proviral DNA)

40
Q

Antivirals

What is the use of integrase strand transfer inhibitors (INSTIs)?

A

HIV-1

41
Q

Antivirals

What is the use of protease inhibitors?

A

HIV-a, hepatitis C, and COVID-19

42
Q

Antivirals

What drugs are neuraminidase inhibitors?

A
  • zanamivir
  • oseltamivir
  • peramivir
43
Q

Antivirals

What drugs are integrase strand transfer inhibitors (INSTIs)?

A
  • raltegravir
  • elvitegravir
  • dolutegravir
  • bictegravir
  • cabotegravir
44
Q

Antivirals

What is the mechanism of action of protease inhibitors?

A

prevent the cleavage of proteins essential to viral replication by competitively blocking the protease binding site

45
Q

Antivirals

What is the catalytic triad involved in the binding of protease inhibitors with protease?

A

Asp81, His57, Ser139

46
Q

Antivirals

What protease inhibitor can treat COVID-19 infection?

A

nirmatrelvir (Paxlovid)

47
Q

Antivirals

What is the use of polymerase inhibitors?

A

herpes simplex virus (HSV), cytomegalovirus (CMV), and herpes zoster virus (HZV)

48
Q

Antivirals

What is the mechanism of action of polymerase inhibitors?

A

block polymerase (viral or cellular) that are essential for the replication = blocks viral replication. these drugs can also bind to the nucleotide binding site to compete with nucleotide binding or allosterically inactivate the target polymerase

49
Q

Antivirals

What drugs are polymerase inhibitors?

A
  • valacyclovir (prodrug)
  • acyclovir
  • valganiclovir (prodrug)
  • ganciclovir
  • famciclovir
  • pencilovir
50
Q

antivirals

What viral polymerase inhibitor is topical due to poor oral absorption?

A

penciclovir

51
Q

antivirals

What is the use of using valacyclovir (prodrug) over acyclovir?

A

better bioavaliability

52
Q

antivirals

What is the mechanism of action of uncoating inhibitors?

A

prevent the extraction of DNA from the viral capsid

53
Q

antivirals

What is the mechanism of action of nucleotide reverse transcriptase inhibitors (NRTIs)?

A

inhibit viral reverse-transcriptase protein thus preventing viral replication

54
Q

antivirals

What NRTI is associated with mitochondrial toxicity?

A
  • stavudine
  • didanosine
55
Q

antivirals

What NRTI is associated with cardiovascular toxicity?

A

abacavir

56
Q

antivirals

What NRTI is associated with renal toxicity?

A

tenofovir

57
Q

antivirals

What is the mechanism of action of foscarnet?

A

pyrophosphate analog that bins to site to block cleavage of deoxynucleotide pyrophosphates to prevent DNA elongation = prevents viral replication

58
Q

antivirals

What drugs are pharmacokinetic enhancers?

A
  • ritonavir
  • cobicistat
59
Q

antivirals

What is the use of ritonavir?

A

boost concentrations of antiviral drugs by inhibiting CYP3A4, and to a lesser extent 2D6, 2C19, 2C8, and 2C9

60
Q

antivirals

What is the use of cobicostat?

A

boost the concentrations of antiviral drugs by inhibiting CYP3A4, and to a lesser extent 2D6

PDA 3 (6 decks)

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