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Flashcards in Pharmacology Deck (83)
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1
Q
35 yo white female presents with weakness, dizziness, and epigastric pain. History of peptic ulcer disease, heavy menstrual bleeding, & chronic headaches. Meds: Tetracycline (ance), Ibuprofen (HA), and Esomeprazole (peptic ulcer dz). Has 2 children in the last 3 years
-Presents: pale, lethargic, looks aged, pale nail beds
-Labs abnormal!:
Hgb 9 (n: 14-18)
Hct 27% (n: 40-44%)
Serum iron 40 (n: 50-160)
Serum ferritin 9 (n: 15-200)
4+ guaiac stools (n=neg)
Which of the listed agents would be given to this patient PO?
A. Ferric gluconate
B. Ferrous sulfate
C. Iron dextran
D. Iron-sucrose complex
E. Sodium ferric gluconate complex
A

B. Ferrous sulfate

For PO option, ferrous is better absorbed (Fe2+)

Note: Proton pump inhibitors and tetracycline may compromise absorption of dietary iron

2
Q
SE of Ferrous sulfate? 
A. Bronchospasm
B. Constipation
C. Fever
D. Hypertension
E. Injection site reactions
A

B. Constipation

Inform pt to take on empty stomach + separately from tetracycline for better absorption
(oral iron therapy may cause nausea, constipation, abd cramps, dark stools)

3
Q
Pt on iron therapy's 1 year old male child presents with vomiting, diarrhea that has become bloody. And x-ray shows he took her pills. Which would be given?
A. Acetylcysteine
B. Activated charcoal
C. Deferoxamine 
D. Flumazenil
E. Pralidoxime
A

C. Deferoxamine (IV, IM) or deferasirox (PO)

(chelating agent for iron)

Activated charcoal..ineffective in iron poisoning

4
Q
6 mo after initiating therapy with ferrous sulfate tx, pt returns with same weakness and dizziness and is more fatigued, still pale, lethargic, + pale nail beds. Pt admits that she missed some doses but still takes peptic ulcer drugs. Stool positive for occult blood. Candidate for which therapy?
A. Cyanocobalamin
B. Deferasirox
C. Epoetin alpha
D. Folic acid
E. Iron dextran
A

E. Iron dextran (IM and IV available)

5
Q

Parenteral iron therapy is indicated for which pts?

Formulated to avoid severe toxicity of free ferric iron upon admin

Bypasses irons storage regulatory mechanisms of the intestine and can deliver more iron than can safely be stored

A

Pts documented with iron def who are unable to tolerate or absorb oral iron and for those with chronic extensive chronic anemia who cannot be maintained with oral iron alone

Indicated for pts with :

  • excessive continuing blood loss
  • IBD
  • Chronic kidney dz
  • Cancer
  • Malabsorption conditions
6
Q
35 yo male with 25 year history of diabetes mellitus diagnosed with renal failure and placed on hemodialysis 3x weekly. Throughout the year, he undergoes numerous blood transfusions to correct his anemia and becomes dependent on the transfusions. Complains of constant fatigue, poor appetite, + low energy. Lab values consistent with renal failure.
-Labs:
Hbg 8 (n:14-18)
Hct 26% (n:42-52%)
Ferritin 360 (n: 15-200)
Serum iron 98 (n: 50-160)
Production of which hematopoietic growth factor is most likely reduced in this pt? What tx is most likely to correct this pt's anemia and is the most appropriate?
A. Cyanocobalamin
B. Darbepoetin alpha
C. Filgrastim 
D. More transfusions
E. Oprelvekin
A

Erythropoetin
(primarily made by kidneys so decreased)

Answer: B. Darbepoetin alpha (stimulate hematopiesis)

(Filgrastim: myeloid growth factor (not w/ AML, CML), neutropenia)
Oprelvekin: megakaryocyte growth factor (IL-11), thrombocytopenia)

note: Transfusions are associated with increased risk of hepatitis, viral infections, iron overload,
treatment‐related acute lung injury, and immunogenic reactions

7
Q

Epoetin alpha, darbepoetin alpha, methoxy polethylene glycol-epoetin beta are all forms of what?

A

Erythropoietin

produced by kidney

8
Q

-Indicated for use in anemia associated with end‐stage renal disease, drug‐induced
anemia (e.g., chemotherapy, zidovudine), AIDS, patients with low endogenous EPO
levels, autologous blood transfusions

-Nearly always coupled with oral or parenteral iron supplementation in patients
with chronic kidney disease

A

Erythropoietin

  • Epoetin alpha
  • darbepoetin alpha
  • methoxy polyethylene glycol‐epoetin beta
9
Q

Darbepoetin alpha is administered at dose of 0.45 mcg/kg. The pt responds appropriately with a dose-dependent rise in Hct. Which drug-related adverse effect is most likely?

A. Black stools
B. Bone pain
C. Cough
D. Hypertension
E. Malignancies
A

D. Hypertension

(kidneys making renin, angiotensin, ADH sys so that is not normal, unable to regulate BP well, so now erythropoetin are there to cause cardiovascular effects, also increases blood viscosity

10
Q

Erythropoietic stimulating agents (ESAs) used cautiously in the clinic…why?

A
  • Increased mortality in diseases such as cancers
  • Not recommended for anemic pts who are not receiving chemotherapy or radiotherapy
  • Increased risk of death by cardiovascular events when ESAs used to increase Hgb
  • HTN, Thrombotic complications
11
Q

41 yo female begins 1st course of adjuvant chemo for metastatic breast cancer. Following premedication with Ondansetron, she receives a combo of doxorubicin, cyclophosphamide, fluorouracil (anti-neoplastic drugs).24 hrs later, she starts a 10-day regimen of filgrastim. Why?

A. Control of nausea and emesis
B. Prevent doxorubicin‐induced cardiotoxicity
C. Reduce the risk and severity of chemotherapy‐induced neutropenia
D. Stimulate the gastric mucosa to repair damage caused by the chemotherapy
drugs
E. Stimulate the production of red blood cells

A

C. Reduce the risk and severity of chemotherapy‐induced neutropenia

12
Q

55 yo female presents with 3 wk hx of frequent stools (3-5/day) with bright red blood. Lethargy, dizziness, ataxia, paresthesias in hands and feet. 9 mo prior, reported progressive confusion and lethargy, but a CBC revealed only mild leukocytosis. Bone marrow aspirate shows megaloblastic blood cell precursors. Which lab value is most expected?

A. Bilirubin – 0.5 mg/dL (n: 0.1‐1.0 mg/dL)
B. B12 – 94 pg/mL (n: 200‐1000 pg/mL)
C. Erythropoietin – 20 mU/mL (n: 4‐26 mU/mL)
D. Folate – 0.5 ng/mL (n: 2‐20 ng/mL)
E. Hgb – 12 g/dL (n: 12‐16 g/dL)

A

B. B12….can cause megaloblatic anemia and presents with neuro issues

-Bilirubin – elevated in pernicious anemia
-Erythropoietin – may be elevated to make up for blood loss; elevated in chemotherapy‐induced anemia;
depressed in anemia of chronic disease
-Folate – deficiencies cause pernicious anemia but without the neurological symptoms
-Hgb – may be lower due to recent blood loss

13
Q
  • Results from impaired DNA synthesis in replicating cells leading to a large immature nucleus.
  • Clinical effects of vit B12 and folic deficiencies can occur.
A

Megaloblastic anemia

14
Q

Tx for megaloblastic anemia?

A
-Low vitamin B12, then  vitamin
B12 supplementation (Cyanocobalamin and hydroxocobalamin)

-Low folic acid – folic acid supplementation (No effect on the neurological symptoms associated with megaloblastic anemias even
though it will largely correct the anemia caused by the vitamin B12 deficiency)

-Again, determine whether malabsorption is an issue (PO vs. IV)

15
Q

For the following hematopoietic GF, what clinical condition is being treated or prevented? Who are the recipients?

Erythropoietin, darbepoetin alfa

A

Anemia

•Patients with chronic renal failure
•HIV‐infected patients treated with zidovudine
•Cancer patients treated with myelosuppressive cancer
chemotherapy
•Patients scheduled to undergo elective, noncardiac,
nonvascular surgery

16
Q

For the following hematopoietic GF, what clinical condition is being treated or prevented? Who are the recipients?

Filgrastim: Granulocyte colony-stimulating factor (G-CSF)

Sargramostim: Granulocyte-macrophage colony stimulating factor (GM-CSF)

A

Neutropenia (cancer pts treated w/ myelosuppressive cancer chemo)

Stem cell or bone marrow transplantation

Mobilization of peripheral blood progenitor cells (PBPC’s) (transplants)

17
Q

For the following hematopoietic GF, what clinical condition is being treated or prevented? Who are the recipients?

Oprelvekin (IL-11 )

A

Thrombocytopenia

Patients with nonmyeloid malignancies who receive
myelosuppressive cancer chemotherapy

18
Q

For the following hematopoietic GF, what clinical condition is being treated or prevented? Who are the recipients?

Romiplostim

A

Thrombocytopenia

Patients with idiopathic thrombocytopenic purpura

19
Q

What are the 3 oral iron drugs?

A
  • Ferrous sulfate
  • Ferrous gluconate
  • Ferrous fumarate

(Only ferrous salts should be used because ferrous iron is most efficiently absorbed)

20
Q

What are the 3 parenteral iron drugs?

A
  • Iron dextran (IM or IV, hypersensitivity rxns)
  • Iron-sucrose complex (IV)
  • Sodium ferric gluconate complex (IV)
21
Q

What are the 2 iron chelators that may be used in iron overdose?

A
  • Deferoxamine

- Deferasirox (reduces liver iron)

22
Q

What are the two B12 drugs?

A
  • Cyanocobalamin

- Hydroxocobalamin

23
Q

What are the two erythrocyte-stimulating agents

A
  • Epoetin alpha (Epogen, Procrit)

- Darbepoetin alpha

24
Q

What are the two myeloid growth factors that are granulocyte stimulating? (G-CSF)

A

Filgrastim (Neupogen)

Pegfilgrastim

25
Q

What is the myeloid growth factors that are granulocyte-macrophage stimulating? (GM-CSF)

What are the SE?

A

Sargramostim

Can cause fever, malaise, arthralgias, myalgias, and a capillary leak syndrome
characterized by peripheral edema and pleural or pericardial effusions so not used as much as the G-CSF drugs!

26
Q

What are the two megakaryocyte growth factors?

A

Oprelvekin (IL-11 b)

Romiplostim

27
Q

Increased erythropoiesis is associated with an increase in the number of ________ receptors on developing erythroid cells

A

transferrin

28
Q

Iron store depletion and iron deficiency anemia are associated with an increased concentration of serum _________

A

transferrin

29
Q

What drug can be used in pts that dont respond to G-CSF alone?

A

Plerixafor

Results in mobilization of hematopoietic stem and progenitor cells from bone marrow
into peripheral blood

Use in combination with filgrastim

30
Q

What is the MOA of Oprelvekin (IL-11)?

A

Stimulate the growth of primitive megakaryocytic progenitors; increases the number of peripheral platelets and neutrophils

31
Q

Which drug is a recombinant thrombopoeitin?

A

Romiplostim

Sctivates Mpl thrombopoietin receptor to cause a dose-dependent increase in
platelet count

32
Q

What are the SE of Oprelvekin (IL-11)?

A

-Fatigue, headache, dizziness, and cardiovascular effects
(e.g., anemia, dyspnea,
transient atrial arrhythmias) are the most common
-Hypokalemia

33
Q

What are the 5 first line NRTIs?

A
Abacavir (ABC)
Emtricitabine (FTC)
Lamivudine (3TC)
Tenofovir (TDF)
Zidovudine (ZDV)
34
Q

What is the mechanism of NRTIs?

A

Host cells metabolize NRTIs to nucleoTide triphosphates, which is blended into pools of natural dNTPs for DNA synthesis. NRTI triphosphate gets “perceived” as a natural dNTP by viral DNA polymerase (HIV reverse transcriptase), and is errantly used for viral DNA synthesis.

1) Competitively inhibit DNA pol
2) Irreversibly “terminate” DNA strand elongation if they incorporate into viral DNA

35
Q

TQ
NRTI-TPs terminate viral DNA synthesis because they lack what?
What does this result in?

A

NRTI-TPs lack a 3’ hydroxyl group (it’s a 3’ sulfur group), resulting in a truncated HIV DNA containing NRTI.

36
Q

What is the NRTI “black box” warning?

A

Lactic acidosis syndrome

37
Q

TQ
Case: A 51-year-old man with HIV infection on highly active antiretroviral therapy presented with abdominal pain & exertional dyspnea. Physical examination revealed increased respiration and cachexia. Laboratory tests showed a lactic acid concentration elevated to 6.4 mM.

Possible questions:
Which of the following classes of antiretroviral therapy is responsible?
Which drug is responsible?

A

NRTIs

any NRTI

38
Q

TQ

What is the treatment for lactic acidosis?

A

IV and oral bicarbonate, riboflavin, and phosphorus supplementation

39
Q

TQ

The hallmark toxicity of NRTIs - as a class - is _____________ toxicity. Why?

A

MITOCHONDRIAL toxicity

HIV reverse transcriptase and the host’s mitochondrial DNA polymerase-(gamma) look very similar, therefore host mitochondria will be target indirectly&raquo_space; Lactic acidosis

40
Q

Impaired _________ _______________ leads to lactate acidemia / acidosis.

Why?

A

Impaired OXIDATIVE PHOSPHORYLATION leads to lactate acidemia / acidosis.

Anaerobic conditions (or disruption of the oxidative phosphorylation system) favor conversion of pyruvate to lactate.

41
Q

TQ

Which NRTI is most likely to cause lactic acidosis (inhibit mt DNA pol-(gamma))?

A

Worst:
Didanosine (ddI) >
Stavudine (d4T) ≥
Zidovudine (ZDV)&raquo_space;>

42
Q

Pt is on highly active antiretroviral therapy and has hepatic steatosis, lipoatrophy/lipodystrophy, pancreatitis…

What would you give the pt in an acute setting?

A

IV bicarbonate
-Must realize that the pt probably already has lactic acidosis acutely; therefore, give something that will manage the acute issue.

43
Q

TQ

Which NRTI is the most nephrotoxic? Why?

A

Tenofovir (TDF) – has a phosphate in the parent molecule (nucleoTide).
Tenofovir is eliminated via glomerular filtration and active tubular secretion. Because of the risk of nephrotoxicity from tenofovir in patients with renal insufficiency an alternative NRTI not associated with renal toxicity, such as abacavir, is preferred.

44
Q

An idiosyncratic, multisystem inflammatory (hypersensitivity) reaction occurs due to what NRTI?

TQ
The genetic test to predict the likelihood of a person developing hypersensitivity looks for what marker?

A

Abacavir (ABC)

HLA-B*5701

45
Q

T/F: As a class, NRTIs have FEW clinically significant drug-drug interactions.

A

TRUE, because they’re not substrates, inhibitors, or inducers of hepatic CYP450 enzymes. NRTIs are mainly eliminated renally .

46
Q

Would you ever use a triple nucleoside analog combination?

A

NO NO NO!
Using 2 together is bad enough… using a combo of 3 NRTIs will undoubtedly have problems involving mitochondrial toxicity or antagonism.

47
Q

TQ
What is the “preferred” NRTI combo for the treatment-naive pt because of its overall potency, favorable toxicity profile, and convenient dosing?

A

Tenofovir / Emtricitabine

[ TDF / FTC ]

48
Q

TQ

What is an “acceptable” NRTI combo, but is also “preferred” in pregnancy?

A

Zidovudine / Lamivudine

[ ZDV / 3TC ]

49
Q

What is an “alternative” NRTI combo?

A

Abacavir / Lamivudine

[ ABC / 3TC ]

50
Q

What is the first line “preferred” NNRTI?

A

Efavirenz

51
Q

TQ
What are the 2 first line “alternatives” in the NNRTI class?
Which is acceptable in pregnancy?
Which is used if resistance develops with other NNRTI?

A

Nevirapine (used in pregnancy)

Etravirine (if resistance develops with other NNRTI)

52
Q

What is the mechanism of NNRTIs?

A
  • Bind and distort reverse transcriptase (RT) enzyme

- Inhibited RT cannot make viral DNA

53
Q

How do NNRTIs inhibit RT?

A

Allosteric inhibition – binding changes the conformation of RT

54
Q

TQ
Because of potential teratogenicity, efavirenz should not be initiated during the first 8 weeks of pregnancy (the primary period of fetal organogenesis). What is the “acceptable” drug in this case?

A

Nevirapine (NVP)

55
Q

All NNRTIs have been assoc with what adverse effect?

Which drug is the worst?

A

Rash and hypersensitivity

Worst = Nevirapine

56
Q

TQ

NNRTIs administration has toxic effects on what organ?

A

Liver

NNRTIs may cause severe and life-threatening hepatotoxicity.

57
Q

The NNRTI which cause the most elevation in liver enzyme is what?

A

Nevirapine >

Efavirenz, Delavridine

58
Q

TQ
The NNRTIs are potent agents, but have a low genetic barrier to resistance; efavirenz, nevirapine, and delavirdine require only a single mutation in reverse transcriptase to confer drug resistance.

What is the signature mutation?

A

K103N

Lysine to Glutamine

59
Q

TQ

Which NNRTI has activity against HIV strains resistant to other NNRTI?

A

Etravirine

60
Q

TQ

What is the “preferred” initial therapy (NRTI pair + NNRTI)?

A

Tenofovir / Emtricitabine + Efavirenz

[ TDF / FTC + EFV ]

61
Q

TQ

Which NNRTI do you always want to avoid in pregnancy?

A

Efavirenz

Use Nevirapine in pregnancy.

62
Q

TQ
What are the 2 first line Protease Inhibitors (PIs)?
What drug is always used as adjunct?

A

Atazanavir (ATV)
Darunavir (DRV)

Adjunct: Ritonavir (r)

63
Q

Which first line PI causes hyperbilirubinemia?

A

Atazanavir (ATV)

64
Q

Which alternate PI may cause diabetes / insulin resistance?

A

Lopinavir (LPV)

65
Q

What the 2 PIs used for drug-resistant HIV?

A

Darunavir (DRV)

Tipranavir

66
Q

Indinavir is now used infrequently because it causes what?

A

Kidney stones

67
Q

TQ
HIV Protease Inhibitors mimic the peptide bond between phenylalanine and proline at positions 167 and 168 of the gag-pol polyprotein.

What type of protease is an HIV protease?

A

ASPARTYL protease

68
Q

TQ

What is unique about Ritonavir (RTV) and why is it always used as an adjunct?

A

Ritonavir (RTV) inhibits CYP3A4 and therefore “boosts” the circulating level of other PIs and prolongs their half-life.

69
Q

TQ

What is the potential problem with Ritonavir?

A

Drug interactions due to CYP3A4 inhibition

70
Q

Which 3 PIs may provoke sulfonamide hypersensitivity?

A

Darunavir
Fosamprenavir
Tipranavir

71
Q

What is the current clinical use of PIs?

What is the preferred regimen?

A

Combination therapy with 2 NRTIs

TDF / FTC + ATV/r
TDF / FTC + DRV/r

72
Q

TQ
What are the 2 regimen options of 2-drug Post-Exposure Prophylaxis (PEP)?
Which is preferred?

A

1) Zidovudine + Lamivudine

2) Tenofovir + Emtricitabine (preferred)

73
Q

TQ

What is the preferred 3-drug (actually 4) regimen for Post-Exposure Prophylaxis (PEP)?

A

Tenofovir + Emtricitabine (NRTIs)
+
Lopinavir + Ritonavir (PIs)

74
Q

TQ

What is the overall preferred regimen in HIV+ pregnant women?

A

Zidovudine/Lamivudine + Lopinavir/Ritonavir

75
Q

What is the generic name of the HIV Integrase Inhibitor (II)?

A

Raltegravir

76
Q

Raltegravir is typically used in pts that have what?

A

Diabetes or lipid problems

Raltegravir doesn’t have an impact on lipids!

77
Q

What is the generic name of the CCR5 antagonist?

A

Maraviroc

78
Q

What is the generic name of the GP41 antagonist?

A

Enfuvirtide

79
Q

TQ

What is the mechanism of maraviroc?

A

Maraviroc blocks the binding of the HIV outer envelope protein gp120 to the CCR5 receptor and prevents downstream events (gp41 exposure and viral fusion)

80
Q

What Fusion/Entry Inhibitor is used against viruses that have become resistant to antiretroviral agents of other classes?

A

Maraviroc

81
Q

TQ
Maraviroc is specific for which receptor?

Maraviroc is ineffective vs HIV strains with gp120 that bind to what receptor?

A

Maraviroc is specific for CCR5.

Ineffective vs HIV strains with gp120 that bind to CXCR4.

82
Q

TQ
One Fusion/Entry Inhibitor has been used in phase 3 clinical trials involving “heavily pretreated patients with multidrug-resistant HIV-1.”

Which Fusion/Entry Inhibitor?

A

Maraviroc

83
Q

TQ

What is the mechanism of Enfuvirtide?

A

Enfuvirtide is a gp41 antagonist, which prevents fusion and entry of HIV into host CD4 cells.