Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

BIIC > Pharmacology > Flashcards

Pharmacology Flashcards

1
Q

Iron salt supplements

A 
1. Ferrous (Fe2+)
  A. Sulfate
  B. Gluconate
  C. Fumerate
  D. Lactate
2. MOA: iron replacement
3. Pharmacokinetics
  A. Take on empty stomach (1hr before meals)
  B. Adjust dose w/ tolerance
  C. OJ inc absorption (ascorbic acid-rich)
  D. Antacids, eggs, milk, coffee, and tea dec absorption
4. Pregnancy category: A
5. Indications: 
  A. Iron deficiency
  B. Fatigue
  C. Supplementation in pregnancy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Iron salt supplement ADRs and considerations

A
  1. Common
    A. Abdominal pain
    B. Constipation
    C. Nausea
    D. Vomiting
  2. Serious: GI bleed
  3. Black box warning: OD fatal in kids
  4. Considerations
    A. Don’t take w/in 4 hrs of levothyroxine
    B. Don’t take w/in 2 hrs of tetracycline
    C. Not for pts w/ hemochromatosis: inc risk toxicity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Nutritive agent Vitamin B12

A
  1. Vit B12 deficiency = Macrocytic anemia
  2. MOA: cyanocobalamin = B12 w/ hematopoietic activity
    A. Works w/ folate -> binding block DNA/RNA
    B. Maintain neurologic system
    C. FA biosynthesis and energy production
  3. Pharmacokinetics
    A. IM injections: 1000-2000 mcg -> hematologic and neurologic response
    B. Oral 1000 mcg: used when B12 marginally low
    C. Nasal spray: pts in remission w/o nervous system involvement
  4. Pregnancy category: C
  5. Indications:
    A. Vit B12 deficiency
    B. Pernicious anemia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Nutritive agent Vitamin B12 ADRs and considerations

A 
Well-tolerated
1. Common
  A. Asthenia: weakness
  B. Headache
2. Serious: rare
  A. Hyperuricemia
  B. Hypokalemia
3. Considerations
  A. Nasal: 1 hr before/after eating hot foods/liquids
  B. Extended-release tablets: take w/ food
    1. Not w/in 2 hrs of other meds
  C. Avoid alcohol
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Nutritive folic acid

A
  1. Folic acid deficiency = Macrocytic anemia
  2. MOA: folic acid -> tetrahydrofolic acid
    A. Erythropoiesis
    B. Purine and thymidylate synthesis
    C. AA metabolism (Gly, Met, His)
  3. Pharmacokinetics
    A. Non-toxic at high doses - excreted in urine
    B. Oral
    1. 1mg/day = replace
    2. 1-5 mg/day = malabsorption
      C. Parenteral- used rarely
  4. Pregnancy category: A
  5. Indications
    A. Folic acid deficiency
    B. Megaloblastic anemia
    C. Pregnancy vitamin
    D. Dec toxicity of methotrexate
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Nutritive folic acid ADRs and considerations

A 
Well-tolerated
1. Common
  A. Bad taste in mouth
  B. Dec appetite
  C. Nausea
  D. Confusion
  E. Sleep-pattern disturbance
2. Serious: allergic rxn
3. Considerations: avoid alcohol
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Erythropoietic agents

A
  1. Epoetin Alfa (t1/2 = 4-13 hrs)
  2. Darbepoetin Alfa (t1/2 = 74 hrs)
  3. MOA: acts as EPO -> stimulate RBC production
  4. Pregnancy category: C
  5. Indications:
    A. Anemia from chemo
    B. HIV
    C. Chronic kidney disease
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Erythropoietic agents ADRs and considerations

A 
1. Common
  A. Nausea
  B. Vomiting
  C. Pruritus
  D. Arthralgia
  E. Myalgia
  F. Headache
  G. Fever
2. Serious
  A. HTN
  B. Inc risk CV event
3. Black box warning: inc risk death, MI, stroke, other CV events
4. Considerations: 
  A. Caution in pts w/ uncontrolled HTN
  B. Can cause iron deficiency
5. Monitor Hb
  A. Don’t exceed 12 g/dL w/ tx 
  B. Doesn’t rise >1 g/dL every 2 weeks
  C. Associated w/ inc mortality and CV events
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Hydroxyurea

A 
Antimetabolite
1. MOA: in sickle cell -> HbF synthesis
  A. Hypothesis: blocks division HbS expressing precursors and stimulates HbF expression
2. Pharmacokinetics
  A. T1/2 = 2-4.5 hrs
  B. Renal excretion: 40% unchanged
  C. Liver metabolism: 60%
3. Pregnancy category: D
4. Indications: 
  A. Sickle cell anemia
  B. Essential thrombocythemia 
  C. Chronic myeloid leukemia
  D. Squamous cell carcinoma head and neck
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Hydroxyurea ADRs and considerations

A 
1. Common
  A. Myelosuppression
  B. Neutropenia
  C. Dec platelets
  D. Dec reticulocytes
2. Serious
  A. Lower extremity ulcers
  B. Skin cancer
3. Black box warning: severe myelosuppression
4. Considerations: 
  A. Inc HbF to 20%+
  B. Dec painful crises 50%
  C. Dec transfusions needed
  D. Doesn’t prevent end-organ damage or stroke
  E. Protect against sun exposure
  F. HbS -> HbF induction slower than 5-azacytidine
  G. Safe used long-term
  H. Monitor HbF every 3-4 mo
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Antineoplastic Agents

A
  1. 5-azacytidine (t1/2 = 4 hrs)
  2. Decitabine (t1/2 = 0.54 - 0.62 hrs)
  3. MOA: DNA methylation agents
    A. Reverse methylation gamma-globin gene
    B. Induce HbF production
  4. Pharmacokinetics
    A. 5-azacytidine: excreted renally
    1. 50% sub-q
    2. 85% IV
      B. Decitabine: excreted renally
  5. Pregnancy category: D
  6. Indications:
    A. Myelodysplastic syndrome
    B. Refractory anemia
    C. Chronic myelomonocytic leukemia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Antineoplastic Agents ADRs and considerations

A 
1. Common
  A. Constipation
  B. Diarrhea
  C. Dec appetite
  D. Nausea
  E. Vomiting
  F. Headache
  G. Fatigue
  H. Fever
  I. Peripheral edema
2. Serious: atrial fibrillation
3. Considerations
  A. Inc HbF synthesis 20%+ in sickle cell pts
  C. Concern about prophylactic use because they are cytotoxic drugs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Colony stimulating factors

A
  1. Filgrastim (t1/2 = 3.5 hrs)
  2. Pegfilgrastim (t1/2 = 15-80 hrs)
  3. Sargramostim (t1/2 = 3.84 hrs IV, 1.4 hr subQ)
    A. GM-CSF: all WBCs
  4. MOA: act on hematopoietic cells and stimulate production of WBCs
  5. Pregnancy category: C
  6. Indications:
    A. Neutropenia
    B. Agranulocytosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Colony stimulating factors ADRs and considerations

A 
Well-tolerated
1. Common
  A. Rash
  B. Diarrhea
  C. Bone pain
  D. Headache
  E. Cough
2. Serious: acute resp distress syndrome
3. Considerations
  A. Check CBC and platelet count every 2 wks for first 4 wks to stabilize dose, then once/mo
  B. Pts report resp infection or distress
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Thrombopoietic growth factor

A
  1. Oprelvekin (t1/2 = 6.9 hrs)
  2. MOA: recombinant human IL-11 -> GM-CSF -> thrombopoiesis
    A. Dose-dependent inc platelet count
  3. Pregnancy category: C
  4. Indications: thrombocytopenia (non-lineage specific)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Thrombopoietic growth factor ADRs and considerations

A 
1. Common
  A. Rash
  B. Nausea
  C. Vomiting
  D. Dizziness
  E. Fatigue
  F. Headache
  G. Dyspnea
2. Serious
  A. Atrial arrhythmia
  B. Fluid retention
3. Considerations
  A. Pt. Report fever and signs of infection and significant fluid retention
  B. Useful in pts w/ nonmyeloid malignancies and have significant thrombocytopenia w/ chemo
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Eltrombopag

A 
Thrombopoietin receptor agonist
1. MOA: small-molecule, non-peptide thrombopoietin (TPO) - receptor agonist
2. Pharmacokinetics: 
  A. t1/2 = 21-35 hr
3. Pregnancy category: C
4. Indications
  A. Thrombocytopenia
  B. Aplastic anemia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Eltrombopag ADRs and considerations

A 
1. Common
  A. Fatigue
  B. Myalgia
  C. Diarrhea
2. Serious
  A. Hepatoxicity
  B. Hemorrhage
3. Black box warning: pts w/ chronic Hep C eltrombopag in combo w/ interferon and ribavarin may inc risk of hepatic decompensation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Thrombopoietin receptor agonists

A
  1. Eltrombopag

2. Romiplostim

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Romiplostim

A 
Thrombopoietin receptor agonist
1. MOA: recombinant IgG, Fc-peptide protein binds and activates thrombopoietin receptor and inc platelet production
2. Pharmacokinetics 
  A. T1/2 = 3.5 days
3. Pregnancy category: C
4. Indications: thrombocytopenia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Romiplostim ADRs and considerations

A 
1. Common
  A. Fever
  B. Diarrhea
  C. Nausea
  D. Arthralgia
  E. Myalgia
  F. Fatigue
2. Serious
  A. Hemorrhage
  B. Acute myeloid leukemia
3. Considerations
  A. Inc risk bleeding - pts avoid situations and meds that inc bleeding
  B. Monitor CBC w/ platelet count weekly to stabilize dose, then monthly
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Coagulation cascade

A
  1. Controlled by many substances
  2. Activation of one -> next (cascade effect)
  3. Two pathways
    A. Intrinsic pathway: slower process, begins circ w/ factor XII
    B. Extrinsic pathway: faster process, begins w/ release of tissue factor
  4. Coagulation factor groups
    A. Vit K-dependent factors
    1. Factors II, VII, IX, X
      B. Contact activation factors
    2. Factors XI, XII, prekallikrein, and high-MW kininogen
      C. Thrombin-sensitive factors
    3. Factors V, VIII, XIII, fibrogen
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Recombinant factor VIII

A 
Antihemophilic agent
1. MOA: glycoprotein produced by hamster kidney/ovary cells, temporarily replaces missing clotting factor VIII
2. Pharmacokinetics
  A. T1/2 = 10-14 hrs
3. Pregnancy category: C
4. Indications: 
  A. Hemophilia A hemorrhage
  B. Factor VIII inhibitor disorder
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Recombinant factor VIII ADRs and considerations

A 
1. Common
  A. Injection site rxn
  B. Headache
  C. Antibody dev
2. Serious: anaphylaxis 
3. Considerations
  A. Pts lack response dev inhibitory antibodies against factor VIII
  B. Inhibitors treated w/ immune tolerance therapy which uses very high doses factor VIII
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Recombinant factor IX

A
  1. MOA: coagulation factor IX, recombinant, is used to temporarily replace missing coag factor IX
  2. Pharmacokinetics
    A. T1/2 = 18-25 hrs
  3. Pregnancy category: C
  4. Indications: hemophilia B hemorrhage
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Recombinant factor IX ADRs and considerations

A
  1. Common
    A. Antibody dev
    B. Headache
  2. Serious: anaphylaxis
  3. Considerations
    A. Pts lack response dev inhibitory antibodies against factor IX
    B. Inhibitors treated w/ immune tolerance therapy which uses high doses factor IX
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Tx of antibody inhibitors

A
  1. Neutralizing Ab to factors VIII, IX
  2. Ab dev in subset pts
  3. Most serious complication of factor replacement therapy and associated w/ morbidity and dec quality of life
  4. Two groups
    A. Low-tiger inhibitor: tx w/ 2-3x usual replacement dose and more frequent dosing intervals
    B. High-tiger inhibitor
    1. Impossible to give enough factor to neutralize Ab
    2. Tx w/ agents that bypass factor that Ab directed
      A. Prothrombin complex concentrations
      B. Activated prothrombin complex concentration
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Recombinant vWF

A
  1. MOA: dec factor VIII clearance by acting as carrier protein and protecting factor VIII from rapid proteolysis
    A. Promotes hemostasis by mediating platelet adhesion to damaged vascular subendothelial matrix and platelet aggregation
  2. Pharmacokinetics
    A. T1/2 = 19-22 hrs
  3. Pregnancy category: C
  4. Indications: vWF disease hemorrhage
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Recombinant vWF ADRs and considerations

A 
1. Common
  A. Injection site rxn
  B. Nausea
  C. Vomiting
  D. Vertigo 
2. Serious 
  A. Ab dev
  B. Deep vein thrombosis (DVT)
3. Considerations
  A. Pts lack response dev inhibitory Abs against vWF
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Desmopressin

A 
Vasopressin
1. MOA: synthetic analogue ADH -> H2O conservation in kidneys
  A. Endothelial cells inc plasma factor VIII actively
2. Pharmacokinetics 
  A. T1/2 = 1-3.4 hrs
  B. Renal impairment 4-8 hrs
  C. Renal excreted 52% unchanged
3. Pregnancy category: B
4. Indications
  A. VWF Type I
  B. Hemophilia A w/ factor levels >5%
  C. Diabetes insipidus
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Desmopressin ADRs and considerations

A 
1. Common
  A. Fatigue
  B. Xerostomia 
  C. Pain at injection site
  D. Intranasal
    1. Nose bleeds
    2. Sore throat
2. Serious: hyponatremia
3. Black box warning: hyponatremia
  A. Don’t use for pts w/ <5% factor VIII Ab 
4. Considerations
  A. Preferred over plasma products be dec risk infection
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Corticosteroids

A
  1. Prednisone (t1/2 = 2-3 hrs)
  2. Methylprednisone (t1/2 = 18-36)
  3. Dexamethasone (t1/2 = 4 hrs)
  4. MOA: inhibit inflam response several ways
  5. Pregnancy category: D
  6. Indications
    A. RA
    B. ITP
    C. Others
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Corticosteroids ADRs and considerations

A 
1. Common
  A. Hypothalamic-pituitary-adrenal suppression
  B. Cushing syndrome
  C. HTN
  D. Hirsutism
  E. Electrolyte imbalance
  F. Osteoporosis
  G. Glucose intolerance
  H. Inc susceptibility infections
2. Serious
  A. Cardiac arrest
  B. Impaired wounds healing
3. Considerations
  A. Inc BS and insulin resistance in DM pts
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Ritiximab

A 
Antineoplastic monoclonal Ab
1. MOA: Ab against CD20 protein on B cells
2. T1/2 = 14-62 days
3. Pregnancy category: C
4. Indications
  A. ITP
  B. Lymphomas/leukemias
  C. Graft vs host disease
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Ritiximab ADRs and considerations

A 
1. Common
  A. Nausea
  B. Diarrhea
  C. Peripheral edema
  D. Anemia
  E. Lymphocytopenia
  F. Asthenia 
  G. Resp infections
2. Serious
  A. Progressive multi focal leukoencephalopathy (PML)
  B. Cardiac probs 
  C. Inc liver enzymes
3. Black box warning: fatal rxns w/in 24 hrs infusion
  A. 80% w/ first infection
  B. Monitor after infusion
  C. Reactivation HBV
4. Considerations
  A. Avoid vaccines
  B. Use reliable contraception during and 12 mo after tx
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Immune globin

A 
Immune serum
1. MOA: supplies broad spectrum opsonizing and neutralizing IgG Ab against wide variety bacterial and viral agents
  A. Blockade of Fc-gamma receptors on macrophages is mechanism implicated in beneficial effect of IVIG in autoAb-mediated cytopenias
2. T1/2 = 6 days
3. Pregnancy category: C
4. Indications
  A. ITP
  B. Guillain- Barre syndrome 
  C. Myasthenia gravis
  D. Primary immune deficiency disorder
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Immune globin ADRs and considerations

A 
1. Common
  A. Inc HR
  B. Injection site rxn
  C. Diarrhea
  D. Nausea
  E. Vomiting
  F. Headache
  G. Asthma
  H. Cough
2. Serious
  A. Tachycardia
  B. Thrombosis
  C. Backache
3. Black box warning: thrombosis may occur
4. Considerations 
  A. Avoid vaccines 
  B. Inc platelet count = efficacy
  C. Anti-D appropriate use in Rh (D) (+) pts w/ intact spleen 
    1. Attach RBCs enter spleen and dec amount platelets sequestered in spleen
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Cancer staging

A 
1. T = size of primary tumor
  A. T1-T3
2. N = extent of nodal involvement
  A. N0 = no nodal involvement
  B. N1 = primary nodal chain involved
  C. N2 = primary and secondary nodes
3. M = presence/absence of metastasis 
  A. M0 = no Mets 
  B. M1 = Mets present
4. General staging (I-IV)
  A. I = localized tumor
  B. II/III = local and regional (N1-2)
  C. IV = distant metastasis (M1)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Neoajuvant chemo

A

Given prior to surgery to inc efficacy to resection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

Adjuvant chemo

A

Used to eradicate micrometastatic disease following surgery/radiation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

Palliative chemo

A

Used to dec tumor size and prevent symptoms

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

Cell cycle specific chemo therapies

A
  1. Active in particular phase of cell cycle
  2. Schedule dependent
  3. Usually given over extended period
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

Cell cycle non-specific chemotherapies

A
  1. Kill independently of phase of cell cycle

2. Usually given as bonus injection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

Alkylating chemotherapy agents

A

MOA: alkylation interferes w/ DNA replication -> cell death

  1. Cell cycle non-specific
  2. Nitrogen mustards
  3. Nitrosoureas
  4. Platinum analogs
  5. Non classic
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

Nitrogen mustard agents

A

Alkylating chemo

  1. Mechlorethamine, melphalan
  2. Cyclophosphamide, ifosfamide
  3. Cholorambucil
  4. Thiotepa
  5. Busulfan
  6. Altretamine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

Nitrosoureas

A

Alkylating chemo agents

  1. Cross BBB => treat brain tumors
  2. Carmustine
  3. Lomustine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

Platinum analogs

A

Alkylating chemo agents

  1. Forms intra-strand cross-links
  2. Used for solid tumors
  3. Cisplatin
  4. Carboplatin
  5. Oxaliplatin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

Non classic alkylating agents

A
  1. Decarbazine, procarbazine
  2. Temozolimide
  3. Bendamustine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

Vinca alkaloids

A

MOA: binds to tubulin -I M phase of cell cycle

  1. Vincristine
  2. Vinorelbine
  3. Vinblastine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

Taxanes

A

MOA: inc tubulin polymerization -> changes tubulin fxn -I M phase of cell cycle

  1. Paclitaxel
  2. Docetaxel
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

Antimetabolites as chemo

A

MOA: inhibits enzymes for DNA, RNA, or protein synthesis (S-phase specific)

  1. Folic acid antagonists
  2. Purine antagonists
  3. Pyrimidine antagonists
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

Folic acid antagonists

A

Antimetabolite chemo

  1. Methotrexate
  2. Pemtrexed
  3. Pralatrexate
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

Purine antagonists

A

Antimetabolite chemo

  1. 6-mercaptopurine
  2. Cladribine
  3. Fludarabine
  4. Pentostatin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

Pyrimidine antagonists

A

Antimetabolite chemo

  1. 5-fluorouracil
  2. Capecitabine
  3. Cytarabine
  4. Gemicitabine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

Antibiotics as chemo

A
  1. Bleomycin
  2. Dactinomycin
  3. Anthracyclines
  4. Mitomycin C
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

Bleomycin

A

Antibiotic chemo

  1. MOA: binds to iron, creates free radicals, results in DNA strand breaks
  2. G2 phase specific
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

Dactinomycin

A

Antibiotic as chemo

1. MOA: inhibits RNA polymerase, binds to DNA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

Antracyclines

A

Antibiotic chemo

1. MOA: intercalated into DNA, free radical formation, topoisomerase II inhibitors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

Mitomycin C

A

Antibiotic chemo

1. MOA: alkylating agent

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

L-asparaginase

A

Chemo

1. MOA: enzyme that breaks down L-asparagine, depleting asparagine in cancer cells that cannot produce the amino acid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

Arsenic trioxide

A

Chemo

  1. MOA: inhibits telomerase activity to cause apoptosis and causes DNA strand breaks
  2. Dactinomycin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

Hydroxyurea as chemo

A

MOA: inhibits ribonucleotide reductase

1. S-phase specific

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

Topoisomerase I inhibitors

A 
Chemo
1. MOA: inhibitor of topoisomerase I
2. S-phase specific
  A. Irinotecan
  B. Topotecan
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

Topoisomerase II inhibitors

A 
Chemo
1. MOA: complexes w/ DNA and enzyme topoisomerase II -> DNA strand breaks 
2. S-phase specific
3. Etoposide
4. Teniposide
5. Anthracyclines 
  A. Doxorubicin
  B. Daunorubicin
  C. Idarubicin
  D. Epirubicin
6. Mitoxantrone
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

2% sodium thiosulfate solution

A

Strong nucleophile neutralizes nitrogen mustards

1. ESP when causes extravasation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
66
Q

Cyclophosphamide and ifosfamide ADRs

A

Hemorrhagic cystitis

1. Hydrate to clear bladder mesna

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
67
Q

Cisplatin ADR

A

Kidney damage

  1. Hydrate w/ chloride-containing solns
  2. Amifostine or 2% sodium thiosulfate soln
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
68
Q

Methotrexate

A

Inhibits enzyme dihydrofolate reductase

1. Leucovorin used as rescue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
69
Q

Anthracyline ADR

A

Forms free radicals -> heart damage bc lacks catalase

1. Dexarazoxane = chelating agent dec free radical damage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
70
Q

Prophylactic antimicrobial therapy

A
  1. Immunosuppressive therapy
  2. Cancer pts
  3. Pre-surgical procedures
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
71
Q

Empiric antimicrobial therapy

A

Tx of known/probable infection

1. Agent chosen based on rational judgement and experience, no broad spectrum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
72
Q

Definitive antimicrobial therapy

A

Pathogen ID and susceptibility determined

  1. Dec risk resistance
  2. Dec risk superinfection and opportunistic infection
  3. Dec risk community resistance dec
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
73
Q

Cell wall synthesis inhibitors

A
  1. Weaken cell wall - penicillin binding proteins (PBPs)
    A. On both gram (-) and (+) bacteria
    B. Transpeptidase inhibition: catalase cross-bridge formation
    C. Autolysin activation: break down cell wall segments
  2. 3 steps inhibited
    A. Murein monomer synthesis
    B. Murein monomer polymerization -> glycine backbone
    C. Glycine polymer cross-linking -> peptidoglycan
    1. Transpeptidase rxn
    2. Two Groups of drugs
      A. Beta-lactams
      B. Others
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
74
Q

Cell wall synthesis inhibitor spectrum

A
  1. Many only effective against gram (+)
    A. Gram (-) intrinsically resistant
  2. Some gram (-) express porin channels -> susceptible to some antibiotics
    A. Some lack porin channels (Pseudomonas aeruginosa)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
75
Q

Cell wall synthesis inhibitor resistance mechanisms

A
  1. Altered PBPs (MRSA)
  2. Expression of efflux pumps
  3. Beta-lactamase enzymes degrade beta-lactate drugs
    A. Most S. Aureus and increasing # of strep
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
76
Q

Beta-lactam antibiotics

A

Cell wall synth inhibitors
1. All have beta lactam ring
A. Acetylates PBPs at binding site
1. Inactivated enzyme
B. Spectra and specific properties vary based on R-groups
2. Resistance
A. Beta-lactamases evolved to defend against antibiotics
1. Penicillinase, cephalosporinase
2. Carbapenems largely resistant
B. Chemical modifications to drug structure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
77
Q

Beta-lactamase inhibitors

A 
1. Common
  A. Clavulanic acid/clavunate
  B. Sulbactam
  C. Tazobactam
  D. Avibactam
2. Common combo: amoxicillin/clavunate
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
78
Q

Penicillins

A
  1. Beta-lactam structure
  2. Inc H2O absorption -> cell lysis
  3. Groups
    A. Natural
    B. Anti-staphylococcal
    C. Extended-spectrum
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
79
Q

Penicillin ADRs

A
  1. Principle: allergic rxn
  2. Usually well-tolerated
  3. Hypersensitivity (type 1: immediate rxn)
    A. 10% self-report allergy
    B. Rxns range: rash -> angioedema and anaphylaxis
    C. Cross-allergic rxns between beta-lactam antibiotics
  4. Diarrhea: disrupt normal microbiome
    A. Superinfections (C. Diff)
  5. Nephrotoxicity: acute interstitial nephritis
  6. Neurotoxicity: seizures w/ inc blood levels
    A. Contraindicated w/ epilepsy
  7. Hematologic toxicities
    A. Dec coagulation
    B. Cytopenias (esp >2 weeks)
    C. Monitor blood counts
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
80
Q

Natural penicillins

A 
1. Narrow spectrum
  A. Gram (+)
  B. Sensitive to penicillinases
2. Pneumococcal infections 
  A. Bacterial pneumonia
  B. Meningitis - can cross BBB
3. Gonorrhea: except penicillinase-expressing strains
4. Gas gangrene (C. Perfringens)
5. Syphilis (T. Pallidum)
  A. Single dose IM penicillin G = curative
  B. No resistance reported 
6. Pharyngitis (beta-hemolytic strep)
  A. Single dose IM penicillin G = curative
7. >90% staph aureus strains resistant
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
81
Q

Natural penicillins pharmacokinetics

A
  1. Penicillin G given IV or IM
    A. Penicillin V = stable (PO)
    B. Distributes throughout body
    C. T1/2 = 30 min
    D. Benzathine can stabilize penicillin G for IM repository
  2. All penicillin renally excreted
    A. DDIs
    1. Anti-gout drug probenecid block renal transporters -> inc penicillin t1/2
      B. Dose adjustment for pts w/ dec renal fxn
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
82
Q

Anti-staphylococcal (penicillinase-resistant) penicillins

A
  1. Narrow spectrum: S. Aureus that express beta-lactamases
    A. Methicillin susceptible to all drugs in this class
    B. MRSA resistant to all
  2. Nafcillin, oxacillin (IV), and dicloxacillin (PO)
    A. Short t1/2 => frequent dosing, some pts can’t tolerate IV (phlebitis)
    B. Renal excretion (except nafcillin - biliary)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
83
Q

Anti-staphylococcal (penicillinase-resistant) penicillins ADRs

A 
1. Nafcillin
  A. Neutropenia
  B. Interstitial nephritis
2. Oxacillin: hepatitis
3. Methicillin: acute interstitial nephritis 
  A. Not used anymore
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
84
Q

Extended spectrum penicillins

A
  1. Aminopenicillins

2. Antipseudomonal penicillins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
85
Q

Aminopenicillins

A
  1. Broad spectrum: some gram (-) and most gram (+)
    A. Affinity for porin on gram (-)
  2. Ampicillin
  3. Amoxicillin
  4. Resistance: beta-lactamases
    A. Co-admin:
    1. Amoxicillin/clavulanate (augmentin) - PO
    2. Ampicillin/sulbactam (unasyn) - IV
      B. Some species H. Influenzae -> resistant PBPs
      C. Resistant gram (-)
    3. Pseudomonas
    4. Enterobacter
    5. Klebsiella
    6. Others
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
86
Q

Ampicillin

A

Extended spectrum penicillin - aminopenicillin

1. Drug of choice for L. Monocytogenes + or - aminoglycosides, gentamicin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
87
Q

Amoxicillin

A 
Extended spectrum penicillin - aminopenicillin
1. Used for most upper resp infections
  A. Bacterio-rhinosinusitis
  B. Otitis
  C. Lower-resp infections
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
88
Q

Antipsueodomal penicillins

A
  1. Piperacillin
  2. Renally eliminated
  3. Vancomycin co-admin -> inc acute interstitial nephritis risk
  4. Dec coagulation w/ high doses
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
89
Q

Piperacillin

A

Extended spectrum penicillin - antipseudomonal penicillin
1. Only one available in USA
2. Little gram (+) efficacy
2. Administered as piperacillin/tazobactam (zosyn) - IV/IM
A. Broadens spectrum to include beta-lactamase producing organisms
1. Pseudomonas
2. Klebsiella pneumoniae

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
90
Q

Cephalosporins

A
  1. Beta-lactam drugs
  2. Penicillinase resistant
    A. Not cephalosporinase resistant
  3. 4 generations: vary in spectrum and indication
    A. Plus 5th “anti-MRSA” generation
    B. Inc class = better BBB crossing
    C. Oldest has much more gram (+) activity
    D. Newer has much more gram (-) activity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
91
Q

First generation cephalosporins

A
  1. Cefazolin (IV)
  2. Cephalexin (PO)
  3. Cefadroxil (PO)
  4. Similar spectrum to anti-staphylococcal penicillins
    A. Better tolerated
    B. MSSA
    C. Streptococcal
    D. Other penicillinase-producing strains (not MRSA)
    E. Not pseudomonas
  5. Renal excretion
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
92
Q

1st generation cephalosporin indications

A
  1. UTIs
  2. Staph/strep (cellulitis/soft tissue abscesses)
  3. Oral not used for severe or systemic infections
  4. Cefazolin (IV) penetrates most tissues except BBB
    A. Surgical prophylaxis
    B. Severe staph infections (bacteremia)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
93
Q

2nd generation cephalosporins

A
  1. Cefaclor (PO)
  2. Cefuroxime (PO)
  3. Cefprozil (IV)
  4. Cefoxitin (IV)
  5. Cefotetan (IV)
  6. Spectrum 1st generation + extended gram (-) coverage
    A. Poor activity against enterococci and pseudomonas aeruginosa
    B. Some B-lactamases evolved against 2nd generation
  7. Pharmacokinetics and toxicities vary
  8. All cleared renally
  9. IM is very painful => avoid
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
94
Q

3rd generation cephalosporins

A
  1. Cefotaxime (IV,IM)
  2. Ceftazidime (IV,IM)
  3. Ceftriaxone (IV, IM)
  4. Cefdinir (PO)
  5. Cefodoxime (PO)
  6. Penetrate body fluids and tissues, including CSF
  7. Ceftriaoxone and cefotaxime: neonatal/childhood H. Influenzae
    A. Meningococci
    B. Pneumococci
    C. Risk C. Diff superinfections
  8. Less potent gram (+) activity
  9. High gram (-) activity
  10. Serious infections caused by organisms resistant to most other drugs
    A. Beta-lactamase producing
    1. Haemophilus
    2. N. Gonorrhoeae
  11. Renal excretion
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
95
Q

4th generation cephalosporins

A
  1. Cefepime (maxipime) - IV only
  2. Spectrum = 3rd generation + pseudomonas aeruginosa and multi-drug resistant strains
  3. More resistance to to hydrolysis by beta-lactamases
  4. Distributes in CSF
  5. Renal excretion
  6. T1/2 = 2 hrs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
96
Q

4th generation cephalosporin indications

A
  1. Enterobacter infections
  2. Most non-penicillin susceptible strains of strep
  3. Gonorrhea
  4. Community-acquired pneumonia
  5. Meningitis
  6. UTIs
  7. Strep endocarditis
  8. Lyme disease
  9. Encephalopathy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
97
Q

Anti-MRSA cephalosporin

A 
Ceftaroline (Teflara) - IV
1. Binds mutated PBP that confers resistance to almost all other beta-lactate
2. Spectrum = 3rd generation + MRSA
  A. Mostly used for MRSA
3. Susceptible some beta-lactamases
4. Indications 
  A. Skin/soft tissue infections
  B. Community acquired pneumonia
  C. Off label
    1. Bacteremia
    2. Endocarditis 
    3. Osteomyelitis
5. T1/2 = 2.7 hrs
6. Renal excretion
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
98
Q

Anti-MRSA cephalosporin ADRs

A
  1. Relatively non-toxic
  2. Major contraindication: cross-reactivity w/ penicillins
  3. Cefotetan: anti-vitamin K effects -> bleeding
  4. Disulfiram-like action: block alcohol oxidation -> inc acetaldehyde
    A. Not available in US
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
99
Q

Monobactams

A
  1. Non-penicillin/non-cephalosporin
  2. Azremonam (azactam) - IV
  3. Cayston - nebulized
  4. Narrow spectrum: only gram (-) similar to 3rd generation
    A. Aerobic gram (-): pseudomonas
    B. Highly resistant beta-lactamases
  5. Indications
    A. Pneumonia
    B. Meningitis
    C. Sepsis
  6. Pharmacokinetics
    A. T1/2 = 1-2 hrs
    B. Renal excretion
    C. Penetrates BBB
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
100
Q

Monobactam ADRS

A
  1. Rash
  2. Inc serum sminotransferases
  3. Safe for pts allergic to penicillin
    A. Except ceftazidime
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
101
Q

Carbapenems

A
  1. Non-penicillin/non-cephalosporin
  2. Imipenem/cilastatin (primaxin)
    A. T1/2 = 1 hr
  3. Doripenem
  4. Ertapenem (t1/2 = 4 hrs)
  5. Meropenem
  6. Broad spectrum
  7. Tx for severe pseudomonas-> resistance
  8. All IV
  9. Renal excretion (70%)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
102
Q

Carbapenem indications

A
  1. UTIs
  2. Lower resp tract infections
  3. Intra-abdominal
  4. Gynecological infection
  5. Skin
  6. Soft tissue
  7. Bone
  8. Joint infections
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
103
Q

Carbapenem metabolism

A
  1. Imipenem hydrolyzed -> toxic metabolite in proximal tubular epithelium
    A. Renal dipeptidase
  2. Cilastatin -I renal dipeptidase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
104
Q

Carbapenem ADRs

A
  1. Nause
  2. Vomiting
  3. Seizures
  4. Cross-rxn w/ beta-lactam hypersensitivity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
105
Q

Glycopeptides

A
  1. Non-penicillin/non-cephalosporin
  2. Vancomycin
  3. Dalbavancin
  4. Oritavancin
  5. Teicoplanin
  6. Telavancin
  7. MOA: inhibit cell wall synthesis by -I polymerization into glycine strands
    A. Also -I transpeptidase
  8. Poor oral absorption
  9. Widely distributed
  10. Renal excretion
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
106
Q

Glycopeptide indications

A
  1. Staph/strep in pts w/ penicillin/cephalosporin allergies
  2. Gram (+) and some anaerobes
    A. Skin and soft tissue infections
    B. Ineffective endocarditis
    C. Nosocomial pneumonia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
107
Q

Glycopeptide ADRs

A
  1. Mostly IV vancomycin
  2. Phlebitis
  3. Ototoxicity: rare, dose-related
  4. Nephrotoxicity
  5. Histamine-mediated “red (neck) man syndrome”
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
108
Q

Lipopeptides

A
  1. Daptomycin
  2. Cyclic cmpds w/ lipophilic tail -> disrupts cell wall
  3. Loss of membrane potention
  4. Spectrum similar to vancomycin
    A. Some gram (+) vancomycin resistant strains (VRSA)
  5. Indications
    A. Skin/soft tissue
    B. Bacteremia
    C. Endocarditis
  6. Not effective pneumonia
  7. Renal excretion
  8. ADRS
    A. Myopathy
    1. Monitor CK levels weekly
      B. Allergic pneumonitis w/ prolonged therapy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
109
Q

Foxfomycin

A
  1. Inhibits enopyruval transferase -I UDP-N-acetylmuramic acid
  2. Transported by GLUT system
  3. Gram (+) and (-) organisms
  4. UTIs
  5. Oral bioavailability (40%)
  6. T1/2 = 4 hrs
  7. Renal excretion
  8. Common ADRs
    A. Diarrhea
    B. Vaginitis
    C. Nausea
    D. Headache
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
110
Q

Management of viral infections

A
  1. Vaccines: most effective way of prevention and tax
  2. Pharmacokinetics
    A. Antiviral drugs
    1. Currently 26 (non-HIV) approved in US
    2. All narrow spectrum and relatively
      B. Palliative care = treat symptoms
  3. Immune response stimulation
    A. Shorter illness duration
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
111
Q

Antiviral drugs

A
  1. Most viral infections resolve spontaneously
  2. Inhibit replication = viristatic
    A. Prevent viral load from inc to pathogen-expressive concentrations
    B. Allows innate immune mechanism to neutralize virus
  3. Specific and timely dx crucial
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
112
Q

Stages of viral lifecycle

A
  1. Attachment and penetration
  2. Uncoating viral genome
  3. Synthesis of viral components
  4. Assembly viral particles
  5. Viral release -> other cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
113
Q

Agents for herpes viruses

A
  1. Herpes = DNA virus
  2. Inhibit viral DNA replication
  3. Spectrum: all active against all herpes viruses
  4. Most are nucleoside analogs
  5. MOA: must be activated by viral phosphorylation
    A. Phosphorylase agents mimic endogenous nucleotides
    B. Incorporated into replication viral DNA strand -I viral DNA polymerase
    C. Stops viral DNA synthesis w/o much effect on host cells DNA replication
  6. Acyclovir and valcyclovir
  7. Penciclovir and famiciclovir
  8. Ganciclovir and valganciclovir
  9. Foscarnet
  10. Cidofovir
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
114
Q

Acyclovir (IV) and valacyclovir (PO)

A
  1. Guanosine analogs -I viral DNA synthesis
  2. HSV-coded thymidine kinase monophosphorylation -> active intermediate -> phosphorylated by cellular kinase
    A. HSV-TK affinity for acyclovir 200x > mammalian enzyme
  3. Phosphorylated drug incorporated -> replication viral DNA
    A. Inhibits viral DNA polymerase => terminates synthesis
  4. Active: HSV-1 thru 4
  5. Resistance: altered/deficient TK and DNA polymerase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
115
Q

Acyclovir (IV) and valacyclovir (PO) mechanical detail

A
  1. Nucleosides phosphorylated by cellular enzymes -> nucleotides
    A. Added 5’ -> 3’
    1. Requires -OH group at 3’ end ribose
    2. Acyclovir lacks ribose and 3’ -OH group
  2. Viral TK adds 1st PO4
  3. 2nd PO4 by cellular enzyme -> nucleotide
  4. False nucleotide competes w/ dGTP for viral DNA polymerase
  5. Early termination of viral DNA
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
116
Q

Acyclovir (IV) and valacyclovir (PO) pharmacokinetics

A 
1. Acyclovir (IV)
  A. PO bioavailability = 15-20%
  B. Only anti-HSV IV approved in US
  C. Distributes well - CSF
  D. T1/2 = 2.5-3
2. Valacyclovir: inc absorption 
  A. Hydrolyzed -> acyclovir in intestines and liver
  B. PO bioavailability = 54-70%
  C. Distribution and t1/2 about equal to acyclovir
3. Renal clearance
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
117
Q

Acyclovir (IV) and valacyclovir (PO) ADRs

A

Generally well tolerated
1. Nephrotoxicity: crystalluria or acute interstitial nephritis
A. Usually high IV dose acyclovir
B. Avoided w/ adequate hydration and no rapid infusion rates
2. GI: PO
A. Nausea
B. Diarrhea
C. Vomiting
3. Neurotoxicity
A. Seizures
B. Tremors
C. Neurologic effects
D. Headache headache
4. Hematologic toxicity: TTP w/ valacyclovir in HIV pts
5. Topical: local irritation
6. DDIs
A. Diuretics/nephrotoxins -> inc risk nephrotoxicity
B. Probenecid and cimetidine dec acyclovir clearance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
118
Q

Penciclovir and famiciclovir

A 
Penciclovir = topical
Famiciclovir = PO
1. Acyclic guanosine neucleoside derivative 
2. Indications: HSV-1, HSV-2, and VZV
3. Pharmacokinetics 
  A. T1/2 = 7-20 hrs (longer than acyclovir) 
4. Resistance (rare)
  A. Dec HSV-TK
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
119
Q

Penciclovir and famiciclovir MOA

A
  1. Nucleosides phosphorylated by cellular enzymes -> nucleotides
    A. Added 5’ -> 3’
    1. Requires -OH groups at 3’ end ribose
    2. Drugs lack ribose and 3’ -OH group
  2. Viral TK adds 1st PO4
  3. 2nd PO4 by cellular enzyme -> nucleotide
  4. False nucleotide competes w/ dGTP for viral DNA polymerase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
120
Q

Penciclovir and famiciclovir ADRs

A
  1. Diarrhea
  2. Nausea
  3. Headache
  4. Confusion
  5. Rash
  6. Hives
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
121
Q

Ganciclovir and valganciclovir

A
  1. Ganciclovir (IV) = acyclovir analog
  2. Valganciclovir (PO) = Valyrian ester of ganciclovir
    A. Hydrolyzed -> ganciclovir in intestine and liver
  3. Indications
    A. Fight cytolomegalovirus (CMV) infection and immunocompromised pts
    B. Prophylaxis in transplant pts
  4. Pharmacokinetics
    A. T1/2 = 4 hrs
    B. Renal excretion
  5. Pregnancy category: x
    A. Teratogenic and carcinogenic
    B. Lower selectivity => can affect host cell DNA
  6. Resistance: CMV resistant w/ dec level ganciclovir triphosphate
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
122
Q

Ganciclovir and valganciclovir MOA

A
  1. Nucleosides phosphorylated by cellular enzymes -> nucleotides
    A. Added 5’ -> 3’
    1. Requires -OH groups at 3’ end ribose
    2. Drugs lack ribose and 3’ -OH group
  2. Viral TK adds 1st PO4
  3. 2nd PO4 by cellular enzyme -> nucleotide
  4. False nucleotide competes w/ dGTP for viral DNA polymerase
  5. Early termination of viral DNA
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
123
Q

Ganciclovir and valganciclovir ADRs

A 
1. Myelosuppression: major dose-limiting effect
  A. Severe neutropenia 15-40% pts - sometimes fatal
  B. Thrombocytopenia (5-20% pts)
  C. Made worse by dec renal excretion or ganciclovir 
2. Neurotoxicity
  A. Headache
  B. Behavioral change
  C. Seizure s
  D. Coma
  E. 1/3 pts stop ganciclovir 
3. GI: nausea, vomiting
4. Phlebitis
5. Liver fxn test abnormalities
6. Fever
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
124
Q

Foscarnet

A

IV Pryophosphate derivative
1. Indications
A. HSV infections resistance to acyclovir and ganciclovir
B. Some cidofovir-resistant CMV infections
C. CMV retinitis in immunocompromised pts
2. Resistance: mutation viral polymerase structure
3. Pharmacokinetics
A. T1/2= 3-7 hrs
B. Well distributed - CSF
1. 10-30% deposited in bone matrix (t1/2= several months)
2. Serum levels dec 50% by hemodialysis
3. Renal excretion
4. Synergistic w/ ganciclovir

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
125
Q

Foscarnet MOA

A
  1. Direct inhibition HSV DNA/RNA polymerase: binds pyrophosphate to binding site
    A. Inhibits DNA chain elongation
    B. Prevents cleavage pyrophosphate from deoxynucleotide triphosphates
  2. Doesn’t require kinase activation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
126
Q

Foscarnet ADRs

A 
1. Nephrotoxicity: required pre-hydration w/ normal saline
  A. Inc by co-admin w/ cidofivir
2. Electrolyte imbalances
  A. Hypocalcemia
  B. Hypomagnesemia
  C. Hypokalemia
  D. Dysphosphatemia
3. Anemia
4. Nausea
5. Fever
6. Seizures
7. Dysrhythmia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
127
Q

Cidofovir (IV)

A 
Cytosine nucleotide analog
1. Structure includes PO4 group => doesn’t require kinase activation
2. Additional PO4 groups added by cellular enzymes 
3. MOA: direct -I viral DNA polymerase 
4. Use: 
  A. Ganciclovir-resistant CMV
  B. CMV retinitis in pts w/ AIDS
5. Resistance: cross-resistant w/ ganciclovir 
6. Pharmacokinetics 
  A. Parent drug: t1/2 = 2.6 hr
  B. Active metabolite: t1/2 = 17-65 hrs
  C. Poor CSF distribution
  D. Renal excretion
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
128
Q

Cidofovir (IV) ADRs

A

1.Nephrotoxicity
A. Contraindicated pts renal impairment and taking nephrotoxicity drugs
B. PO probenecid and IV saline co-admin -> dec [cidofovir] secreted -> renal tubules
C. Serum levels dec 75% by hemodialysis
2. Neutropenia (15-24%)
3. Mutagenicity
4. Gonadotoxicity
5. Embryotoxicity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
129
Q

Agents for influenza and RSV

A
  1. RNA viruses
  2. Amantadine and rimantadine
  3. Neuraminidase inhibitors
  4. Baloxivir
  5. Ribavirin
  6. Palivizumab
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
130
Q

Amantadine and rimantadine

A
  1. Prevention and tx influenza A
    A. 70-90% protective
  2. Resistance: common-dev w/in
    2-3 days tx
    A. Amantadine not recommended because of high resistance
  3. Pharmacokinetics
    A. PO - good bioavailability
    B. Amantadine renally cleared
    C. Remantadine hepatically metabolized -> renally cleared
    D. Adjust does for dec renal fxn and pts 65+ y/o
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
131
Q

Amantadine and rimantadine MOA

A

Prevents uncoating

  1. Viral ion channels (M2) allow H+ -> virus after endocytosis -> dissociation virus capsid
  2. Influenza A ribonucleoprotein (RNP) -> host cell cytosol
  3. Drugs block M2 channels
132
Q

Amantadine and rimantadine ADRs

A 
1. Minor dose-related
  A. CNS (amantadine 5-33%)
    1. Nervousness
    2. Light-headedness
    3. Dec concentration
    4. Insomnia
  B. GI
    1. Anorexia
    2. Nausea
2. DDIs
  A. Amantadine + antihistamines, psychotropic, anticholinergic drugs -> inc neurotoxicity
  B. Inc [amantadine] ->
    1. Delirium
    2. Hallucinosis
    3. Seizures
    4. Coma
    5. Arrhythmias
  C. Exacerbate preexisting seizure disorders and psych symptoms
133
Q

Neuroaminidase

A

Virus-specific antigen hydrolytic enzyme
1. Multifunctional
A. Cleaves sialic acid residue from host cell receptors targeted by hemaggutinin => control viral adhesion to host
B. Promote fusion viral envelope w/ host membrane -> viral entry
C. Drug -> release newly formed virus particles
1. Cleaving sialic acid -I hemagglutinin new particles aggregating on cell surface
2. Virus -> other cells

134
Q

Neuroaminidase inhibitors

A
  1. Oseltamivir (PO)
  2. Zanamivir (inhalation)
  3. Peramivir (IV)
  4. Prevent/tx Influenzae A and B, and RSV
  5. Pharmacokinetics
    A. Oseltamivir = prodrug
    1. Hydrolyzed liver -> active form
      B. Renally excreted
  6. Resistance: neuraminidase mutations
  7. Prevent neuraminidase from releasing new viral particles
  8. Prophylaxis for pts who can’t tolerate influenzae vaccine
  9. Admin w/in 24-48 hrs onset symptoms -> dec intensity and duration
135
Q

Neuroaminidase inhibitors ADRs

A
  1. Transient GI discomfort and nausea
  2. Resp tract irritation
    A. Caution pts w/ asthma and COPD (bronchospasm)
136
Q

Baloxivir (PO)

A
  1. Single dose to influenza A and B
  2. FDA approved 10/24/2018
  3. New MOA: viral polymerase acidic proteins (CAP) endonuclease inhibitor
    A. Influenza mRNA requires host mRNA sequence to prime ribosome for translation
    1. CAP endonuclease cleave 5’ host mRNA cap (cap-snatching)
      A. Only infected cells
      B. Inhibits viral replication
  4. ADRs
    A. Headache
    B. Diarrhea
    C. Inc serum ALT and AST (rate 1-4%) - dose dependent
137
Q

Ribavirin

A

Broad-spectrum antiviral agent (PO, inhalation)
1. Uses
A. Mostly used against RSV
B. Combo therapy w/ others for tx hep C virus (oral)
C. Influenza and adenovirus
2. Guanosine nucleoside analog
3. MOA not well known
A. Viral replication inhibited
B. Phosphorylated-> active form in cells
C. Inhibit viral RNA polymerase
D. Deplete GTP -> inc viral mutagenesis
E. Activate immune system
4. Resistance reported
5. Aerosol: tx RXV immunocompromised infants and young kids w/ severe RSV
6. Renally cleared

138
Q

Ribavirin ADRs

A
  1. Dose-dependent hemolytic anemia and inc bilirubin
  2. Aerosol safer but can make resp fxn dec in infants
  3. Pregnancy category: X
    A. Teratogen
139
Q

Palivizumab (IM)

A 
Monoclonal AB directed against A antigenic site RSV F protein -I adhesion and entry into host
1. Only indicated inc risk pads pts 
  A. Very expensive
2. Prophylaxis start RSV season
  A. Premies
  B. Airway abnormalities
  C. Severely immunocompromised 
3. Metabolized by CYP450 pathways 
4. ADRs
  A. Anaphylaxis
  B. Severe thrombocytopenia 
  C. Fever
  D. Rash
140
Q

Antimalarial drugs

A
  1. Inhibitors of heme metabolism
  2. Inhibitors of e- transport
  3. Translocation inhibitors
  4. Folate metabolism inhibitors
141
Q

Heme metabolism inhibitors

A
  1. Quinolones

2. Artemisinin derivatives

142
Q

Quinolones

A 
1. Choloroquine (t1/2 = 45-55 days)
  A. Dose weekly
2. Quinine (t1/2 = 11 hrs)
  A. Dose every 8 days
3. Quinidine (t1/2 = 6-8 hrs)
  A. Dose every 8 hrs
4. Mefloquine (t1/2 = 2-3 wks)
  A. Dose weekly
5. Pharmacokinetics 
  A. Quinine and quinidine not used in G6PD pts because increases accumulation
6. Pregnancy category: C
7. Indications: prevention and tx of malaria
143
Q

Quinolone MOA

A

Accumulates in parasite’s food vacuole and binds heme -I heme polymerization to hemozoin
1. Accumulation of unpolymerized heme -> [O] membrane damage to parasite

144
Q

Quinolone ADRs

A 
1. Common
  A. Cinchonism-A syndrome
    1. Tinnitus
    2. Deafness
    3. Headache
    4. Nausea
    5. Vomiting 
    6. Visual disturbance
    7. Pruritis 
2. Serious: prolonged QT interval
  A. Chloroquine toxic inc doses 
    1. Fatal in kids w/ accidental ingestion
  B. Mefloquine: neuropsychiatric effects
    1. Vivid dreams/nightmares
    2. Insomnia
    3. Anxiety
    4. Depression
    5. Hallucinations
    6. Seizures
145
Q

Quinolone considerations

A
  1. Choloroquine: 1st choice tx and prophylactic
    A. Ineffective resistant strains P. Falciparum
  2. Quinine
    A. In tonic H2O
    B. Prophylactic
    C. DNA intercalator -I DNA synth and dec replication of erythrocytic form of plasmodia
146
Q

Artemisinin derivatives

A
  1. Artemisinin
  2. Artesunate
  3. Artemether
  4. Dihydroarteminisin
  5. Indications: therapeutic tx malaria
  6. Pharmacokinetics
    A. Artesunate and artemether metabolized -> dihydroartemisinin
    B. Co-admin ketoconazole -> dec metabolism artemisinins
    1. Ketoconazole = patent CP3A4 inhibitor
      C. Artemisinin dose daily
  7. Pregnancy category: C
    A. Not recommended 1st trimester
    B. Okay 2nd and 3rd
147
Q

Artemisinin derivatives MOA

A

Activated by iron -> free radical

1. Alkylation heme and proteins -> artemisinin-heme adducts and artemisinin-protein adducts - toxic to plasmodia

148
Q

Artemisinin derivatives ADRs and considerations

A
  1. Better tolerated than other
  2. Common
    A. Nausea
    B. Vomiting
    C. Dizziness
    D. Tinnitus
  3. Type 1 hypersensitivity rxn
  4. Considerations
    A. 1st line tx P. Falciparum
    B. Not effective prophylaxis
    C. Inc risk resistance because short t1/2
    1. Don’t use as monotherapy
      A. Artemether-lumefantrine
      B. Artesunate-mefloquine
      C. Artesunate-amodiaquine
      D. Dihydroartemisinin-piperazine
149
Q

Inhibitors of e- transport

A 
1. Primaquine (t1/2 = 7 hrs)
  A. Daily dose
2. Atovaquone (t1/2 = 2-3 days)
  A. Daily dose
3. Pharmacokinetics 
  A. Primaquine -> quinone (active metabolite)
  B. Not for pts w/ G6PD
4. Pregnancy category: C
  A. Primaquine not recommended
5. Indications: malaria prophylaxis and tx
150
Q

Inhibitors of e- transport MOA

A

Selectively interrupts plasmodia ETC by interfering w/ ubiquinone fxn

  1. Primaquine targets ubiquinone
  2. Atovaquone targets Cyto bc1 complex
151
Q

Inhibitors of e- transport ADRs and considerations

A

Atovaquone > primaquine bc less ADRs
1. Common
A. Abdominal pain
B. Nausea
2. Serious
A. Hemolytic anemia
B. Leukopenia
3. Considerations
A. Primaquine -I hepatic stage P. Vivax and P. Ovale
B. Atovaquone not monotherapy because hight resistance dev
1. Co-admin w/ doxycycline or proquanil

152
Q

Translation inhibitors

A 
1. Doxycycline (t1/2 = 11-23 hrs)
  A. Daily dose
2. Tetracycline (t1/2 = 6-11 hrs)
  A. Dose every 6 hrs
3. Clindamycin
4. Pregnancy category
  A. Tetracycline: D
  B. Clindamycin: B
5. Indications: malaria prophylaxis and tx
153
Q

Translation inhibitor MOA

A

Inhibit parasite protein synth

  1. Tetracyclines, doxycycline: bind 30s ribosomal subunit and blocks binding tRNA to A site mRNA
  2. Clindamycin: binds 50s ribosomal subunit -I transfer a.a. To A site
154
Q

Translation inhibitors ADRs and considerations

A 
1. Tetracycline 
  A. Common
    1. Photosensitivity
    2. Diarrhea
    3. Nausea
    4. Vaginal candidiasis
    5. Tooth discoloration
    6. Bone growth disruption in kids (only used 8+ y/o)
  B. Serious: c. Diff
2. Clindamycin
  A. Well-tolerated, esp kids
  B. Black box warning: C. Diff
3. Consideration 
  A. Combo w/ artesunate or quinine
155
Q

Folate metabolism inhibitors

A 
1. Sulfadoxine (t1/2 = 100-230 hrs)
  A. Single dose for infection
  B. Prophylaxis weekly or biweekly
2. Pyrimethamine (t1/2 = 54-148 hrs)
  A. Single dose for infection
  B. Prophylaxis weekly or biweekly
3. Proquanil (t1/2 = 12-21 hrs)
  A. Daily dose
4. Pregnancy category: C
5. Indications: malaria
  A. Prophylactic
  B. Therapeutic
  C. Sulfadoxine-pyrimethamine used in pts 2+ months
156
Q

Folate metabolism inhibitors MOA

A

Folate needed for DNA synthesis target dihydrofolate reductase (DHFR) and dihydrofolate synthase (DHPS)

  1. Sulfadoxine targets DHPS
  2. Pyrimethamine and proguanil targets DHRF
  3. Useful because humans don’t synthesize folate
157
Q

Folate metabolism inhibitors ADRs and considerations

A 
1. Sulfadoxine-pyrimethamine
  A. Common
    1. Pruritus 
    2. Diarrhea
    3. Nausea
    4. Vomiting
    5. Headache
  B. Black box warning: discontinue w/ rash
    1. Fatalities assoc w/
       A. SJS
       B. Toxic epidermal necrolysis
2. Proguanil
  A. Well tolerates
  B. Common
    1. Abdominal pain
    2. Diarrhea
    3. Nausea
    4. Vomiting 
    5. Pruritis
  C. Serious: hepatitis 
3. Considerations
  A. Combo sulfadoxine-pyrimethamine effective blood schizont stages P. Falciparum
  B. Combo atovaquone-proguanil effective blood schizont stage resistant strains P. Falciparum and P. Vivax
158
Q

Antiprotozoal agents

A 
1. Antibiotic
  A. Metronidazole
  B. Tinidazole
2. Antiprotozoal
  A. Nitazoxanide
3. African sleeping sickness drugs
  A. Pentamidine
  B. Suramin
  C. Melarsoprol
  D. Eflornithine
4. Chaga’s disease drugs
  A. Nifurtimox
5. Leishmania Tx
  A. Sodium stibogluconate and meglumine antimonate
  B. Amphotericin and miltefosine
159
Q

Anitbiotic antiprotozoal agents

A 
1. Metronidazole (t1/2 = 6-12 hrs)
  A. Dosed every 8 hrs
2. Tinidazole (t1/2 = 13-14 hrs)
  A. Dosed daily
3. Pregnancy category: B
4. Indications: wide variety anaerobic protozoan parasites and anaerobic bacteria
  A. T. Vaginalis
  B. E. Histolytica 
  C. G. Lamblia
160
Q

Anitbiotic antiprotozoal agents

MOA

A

Aneirobic pathogen’s ETC donates e- to drugs -> highly reactive nitro radical anion targets DNA -> kills pathogen

161
Q

Anitbiotic antiprotozoal agents

ADRs and considerations

A 
1. Common
  A. Nausea
  B. Headaches
  C. Candida vaginitis
2. Considerations
  A. Useful for trichomoniasis, giardia 
  B. Metronidazole tx amoeba infection but tinidazole ineffective 
  C. H. Pylori resistant metronidazole 
  D. Tinidazole shorter tx course than metronidazole
162
Q

Nitazoxanide

A
  1. MOA: inhibits activity pyruvate: ferredoxin oxidoreductase (PFOR) - needed anaerobic energy metabolism
  2. Pharmacokinetics
    A. Dosed every 12 hrs
    B. Rapidly metabolized -> tizoxamnide (t1/2 = 1-1.5 hrs)
  3. Pregnancy category: b
  4. Indications
    A. Protozoa
    B. Anaerobic bacteria
    C. Helminths
163
Q

Nitazoxanide ADRs and considerations

A 
Well tolerated
1. Common
  A. Abdominal pain
  B. Nausea
  C. Headache
2. Considerations
  A. Giardia lamblia
  B. Cryptosporidium paryum
164
Q

African trypanosomiasis (sleeping sickness) drugs

A 
1. Early stage: no CNS involvement
  A. Pentamidine
  B. Suramin
2. Late stage: CNS involvement
  A. Melarsoprol
  B. Eflornithine
165
Q

Pentamidine

A 
Early stage African sleeping sickness tx
1. MOA: inhibit DNA, RNA, and protein synthesis and -I dihydrofolate reductase
2. ADRs
  A. Fatigue
  B. Dizziness
  C. Hypotension
  D. Pancreatitis
  E. Kidney damage
166
Q

Suramin

A

Early stage African sleeping sickness tx
1. MOA: interacts w/ macromolecules -I energy metabolism and -I RNA polymerase
2. ADRs
A. Pruritus
B. Paresthesia
C. Vomiting
D. Nausea

167
Q

Melarsoprol

A

1st line late stage African sleeping sickness tx
1. MOA: inhibits trypanosomal pyruvate kinase -I glycolysis -I adenine and adenosine uptake by trypanosomal transporters
2. ADRs
A. Toxic to humans (4-6% death rate)
B. Phlebitis
C. Brain inflammation (5-10%)

168
Q

Eflornithine

A
  1. Early and late stage Western African sleeping sickness
    A. Not Eastern
  2. MOA: irreversible -I ornithischians decarboxylase and -I polyamine synthesis -I nuclei acid synthesis and protein synthesis
  3. ADRs
    A. Less toxic than melarsoprol
    B. Acne
169
Q

Nifurtimox

A 
Chaga’s disease tx 
1. MOA: generate toxic ROS in parasites
  A. Parasites lack catalase
2. ADRs
  A. Anorexia
  B. Vomiting
  C. Memory loss
  D. Sleep disorders
  E. Seizures
170
Q

Leishmania tx

A
  1. Sodium stibogluconate and meglumine antimonate
    A. MOA: pentavalent antimony -I glycolysis and F.A. Oxidation
    B. ADRs
    1. Prolonged QT interval
    2. Pancreatitis
    3. Rash
  2. Amphotericin and miltefosine also approved to treat resistant strains
171
Q

Antiheolminthic agents

A
  1. Ivermectin
  2. Albendazole
  3. Mebendazole
  4. Triclabendazole
  5. Praziquantel
  6. Antifilarial agent
    A. Diethylcarbamazine
172
Q

Ivermectin

A

Antihelmintic drug
1. MOA: activate glutamate-gated Cl- channels -I neuromuscular transmission -> paralysis
2. Pharmacokinetics
A. Single dose
B. Retreat wks/months later
3. Pregnancy category: C
4. Indications: microfilariae (immature onchocerca)

173
Q

Ivermectin ADRs and considerations

A
  1. Common
    A. Inflam/allergic rxn to dying microfilariae
    B. Headache
    C. Dizziness
    D. Rash
    E. Pruritis
  2. Serious: seizures (careful w/ epileptics)
  3. Considerations
    A. Macrocytic lactone: broad spectrum helminths and arthropods
    B. Tx for nematode infections in animals
174
Q

Anthelmintics

A 
1. Albendazole (t1/2 = 8-15 hrs)
  A. Dosed daily
2. Mebendazole (t1/2= 1-11 hrs)
  A. Dosed every 12 hrs
3. Triclabendazole (t1/2 = 8 hrs)
  A. Dosed every 12 hrs
4. MOA: binds nematodes beta-tubulin -I polymerization -I motility and DNA replication -> immobilization and death
5. Pregnancy category: C
6. Indications
  A. Tapeworms
  B. Hookworms
  C. Liver flukes
175
Q

Anthelmintics ADRs

A 
1. Common
  A. Vomiting
  B. Nausea
  C. Diarrhea
2. Serious
  A. Inc liver enzymes
  B. SJS
3. Considerations
  A. Pt should use effective contraception during tx and 3 days after
176
Q

Praziquantel

A 
Antihelmintic
1. MOA: inc parasite membrane Ca2+ permeability -> contraction and paralysis or worm
2. Pharmacokinetics 
  A. T1/2 = 0.8-1.5 hrs
  B. Dosed every 8 hrs
  C. 80% renal excretion
3. Pregnancy category: B
4. Indications:
  A. Drug of choice for adult cestode (tapeworm) and trematode (fluke) infections
177
Q

Diethlycarbamazine

A 
Antifilarial agent
1. MOA: unknown- hypothesis:
Stimulate innate immune mechanism, -I microtubule polymerization, or -I arachidonic acid metabolism
2. Pharmacokinetics 
  A. T1/2 = 10-12 hrs
  B. Dosed daily
3. Pregnancy category: X
4. Indications: adult filariasis worms
5. ADRs - well tolerated
  A. Anorexia
  B. Headache
  C. Nausea
178
Q

Antiretroviral Therapy (ART)

A
  1. HIV therapy life-long
  2. Dec viral load over time
    A. Disease from CD4+ T lymphocyte toxicity
  3. Restore and preserve immune fxn
    A. Prevent/delay opportunistic infections
  4. ART tx promotes:
    A. Enhanced survival
    B. Dec morbidity
    C. Dec risk transmission
  5. Immediate ART initiation recommended most cases
  6. Pt adherence essential
  7. Monotherapy not recommended
179
Q

ART classes

A
  1. NRTIs: nucleoside/nucleotide reverse transcriptase inhibitors
  2. NNRTIs: non-nucleotide reverse transcriptase inhibitors
  3. PIs: protease inhibitors
  4. FIs: fusion/entry inhibitors
  5. INSTIs: integrase inhibitors
180
Q

Initial HIV therapy

A

2 NRTIs + 1 of the following:

  1. INSTI
  2. NNRTI
  3. PI + CYP450 inhibitor
181
Q

Prescribing ARTs

A
  1. Avoid same analogs
  2. Avoid overlapping toxicities
  3. Appropriate for genotype and phenotype of virus
  4. Consider pt. Factors
  5. DDIs
  6. Ease of adherence
182
Q

Fixes for failed ATR therapy

A
  1. Boosted PI
  2. Add/change INTI
  3. Add/change NRTIs
  4. Always refer to most current guidelines
183
Q

HIV drugs in pregnancy

A 
1. NRTIs
  A. Abacavir
  B. Emtricitabine
  C. Iamivudine
  D. Tenofovir disoproxil fumarate
  E. Zidovudine
2. NNRTIs
  A. Efavirenz
  B. Rilpivirine (alternate)
3. PIs
  A. Atazanavir/ritonavir
  B. Daranzvir/ritonavir
  C. Lopinavir/ritonavir (alternate)
4. INSTIs
  A. Raltegravir (not recommended 1st trimester - neural tube susceptible)
184
Q

ART common features

A
  1. PO formulation, daily dosing
  2. Effect of food on absorption and bioavailability important
  3. Common ADRs
    A. Headache
    B. Nausea
    C. Vomiting
    D. Diarrhea
    E. Hepatotoxicity
    F. Myelosuppression
  4. Most metabolized or inhibited by CYP enzymes (liver)
  5. DDIs common concerns
185
Q

NRTIs

A
  1. Nucleotide analogs
  2. Competitively inhibit RT
  3. Effective HIV-1 and HIV-2
  4. Agents
    A. Zidovudine (T)
    B. Stavudine (T)
    C. Emtricitabine (C)
    D. Lamivudine (C)
    E. Didanosine (A)
    F. Tenofovir (A)
    G. Abacavir (G)
  5. Must be phosphorylated -> triphosphate active form
    A. Inhibit RT > human DNA polymerase
  6. Accumulate in most dividing cells in body -> ADRs
186
Q

NRTI ADRs

A 
1. All have risk mitochondrial toxicity
  A. Peripheral neuropathy
  B. Pancreatitis
  C. Lipoatrophy
  D. Hepatic steatosis 
2. Lactic acidosis: less common, potentially fatal
  A. Warning signs
    1. Inc aminotransferase levels
    2. Progressive hepatomegaly
    3. Metabolic acidosis w/ unknown cause
187
Q

Zidovudine

A 
NRTI (T)
1. ADRs
  A. Bone marrow suppression
  B. Myopathy
  C. Liver toxicity
  D. Lipoatrophy
  E. Insulin resistance
188
Q

Stavudine

A 
NRTI (T)
1. ADRs
  A. Peripheral neuropathy
  B. Lipoatrophy
  C. Insulin resistance
189
Q

Emtricitabine

A

NRTI (C)
1. ADRs
A. One of least toxic
B. Hyperpigmentation of skin

190
Q

Lamivudine

A

NRTI (C)

1. Least toxic NRTI

191
Q

Didanosine

A

NRTI (A)
1. ADRs
A. Peripheral neuropathy
B. Pancreatitis

192
Q

Tenofovir

A

NRTI (A)
1. ADRs
A. One of lease toxic NRTIs

193
Q

Abacavir

A 
NRTIs (G)
1. ADRs
  A. Hypersensitivity (5% pts)
    1. Fever
    2. Rash
    3. GI symptoms
    4. Malaise
    5. Resp distress
194
Q

NRTI pharmacokinetics

A
  1. Inc fat/acidity of food affects absorption
  2. Plasma t1/2 bs triphosphate t1/2 -> daily dose
  3. Dec plasma protein binding
  4. Renal excretion -> dec DDIs
    A. Except zidovudine and tenofovir
  5. Adjust in renal failure
    A. Except abacavir
195
Q

NNRTIs

A
  1. Not structurally related to nucleosides/tides
  2. Doesn’t need activation
  3. Only effective on HIV-1
  4. Main limitation: resistance dev rapidly
    A. Never use as monotherapy or as single addition to failing therapy
    B. Cross-resistance w/ other NNRTIs
  5. Agents
    A. Efavirenz
    B. Nevirapine
    C. Delavirdine
    D. Etravirine
    E. Rilpivirine
196
Q

NNRTI MOA

A
  1. Bind allosteric sight on HIV-RT -> conformational change -> dec RT activity
    A. (-) allosteric modulation
  2. No activity host DNA polymerase => dec ADRs
197
Q

NNRTI ADRs

A 
Better than NRTIs
1. Common
  A. Hypersensitivity rxn (rash)
  B. Dizziness
  C. Neuropsychiatric effects (efavirenz)
198
Q

Efavirenz

A 
NNRTI
1. ADRs
  A. Neuropsychiatric events
  B. Teratogenic
2. Safe for TB pts 
3. Lower DDIs w/ rifamycins
199
Q

Nevirapine

A

NNRTI
1. Rarely used
A. Toxicity, inferior antiviral activity

200
Q

Delavirdine

A

NNRTI

1. Rarely used (toxicity, inferior antiviral activity)

201
Q

Etravirine

A

NNRTI

  1. Second-generation
  2. Use limited to multi drug-resistant HIV
202
Q

Rilpivirine

A 
NNRTI
1. Recommended for pregnant women
2. ADRs - less than efavirenz
  A. Depression
  B. Insomnia
203
Q

NNRTI pharmacokinetics

A 
1. Food inc absorption
  A. Esp rilpivirine
2. Plasma t1/2 -> daily dosing
3. Moderate -> high plasma protein binding
4. Hepatically metabolized by CYPs
  A. Many -> CYPs and autoinduce 
  B. Inc risk DDIs
204
Q

Fusion inhibitors (FI)

A
  1. Maraviroc

2. Enfuvirtide

205
Q

Maravirov

A

FI
1. Dev when discovered that some HIV+ doesn’t lead to AIDS
A. Deleted CCR5 gene
2. MOA: blockage CCR5 -I attachment and entry
A. CXCR4 strains not susceptible
3. Dec risk transmission

206
Q

Maravirov pharmacokinetics

A 
1. PO
  A. Food dec bioavailability 
2. Metabolized by CYP3A4
  A. Inc dose w/
    1. Efavirenz 
    2. Etravirine 
    3. Strong CYP450 inducers
  B. Dec dose w/
    1. Most PIs
    2. CYP450 inhibitors
3. Eliminated thru feces
  A. 20% renal clearance
  B. Contraindicated severe/end-stage renal impairment 
  C. Caution dec hepatic fxn
207
Q

Maravirov ADRs

A
  1. Severe hepatotoxicity
    A. Liver monitoring
  2. Upper resp infections
208
Q

Enfuvirtide

A 
FI
1. Polypeptide
2. Binds HIV-1 gp41 -I conformational change -I entry
3. Indicated tx- experienced pts w/ viral load w/ other tx 
4. Use in combo w/ other agents 
5. Pharmacokinetics 
  A. SubQ
  B. T1/2 = 3.8 hrs
  C. Metabolized proteolytic hydrolysis
6. ADRs: related to injection
  A. Pain
  B. Erythema
  C. Induration
  D. Nodules (occurs in all pts)
209
Q

Protease inhibitors (PI)

A 
1. Reversible HIV aspartyl protease inhibitors
  A. Prevent cleaving HIV proteins needed for maturation
2. Guidelines prefer
  A. Atazanavir
  B. Darunavir
3. Inc genetic barrier to resistance 
4. Recommended initial regimens in pts w/ uncertainties
  A. Adherence
  B. Resistance testing results not yet available 
5. Agents
  A. Atazanavir
  B. Ritonavir
  C. Darunavir 
  D. Fosamprenavir
  E. Indinavir
  F. Lopinavir and ritonavir
  G. Saquinavir
  H. Tipranavir
  I. Neflinavir
210
Q

PI ADRs

A 
1. Common (dec w/ atazanavir and darunavir)
  A. Nausea
  B. Diarrhea
  C. Abdominal pain
  D. Vomiting
2. Glucose/lipid metabolism disturbance
  A. Insulin resistance
  B. Diabetes
  C. Hyper triglycerides 
  D. Hypercholesterolemia
3. Fat redistribution
  A. Extremities -> abdomen, base of neck (buffalo hump), and breasts
211
Q

PI pharmacokinetics

A
  1. Food inc absorption
  2. T1/2 varies
    A. Often given w/ booster
  3. Inc protein binding
  4. Elimination CYP metabolism
    A. DDIs big concern
212
Q

PI DDIs

A 
1. PIs = substrates and potent CYP450 inhibitors 
  A. Substrates of P-gp efflux pump
2. Contraindicate all PIs
  A. Rhabdomyolysis
    1. Simvastatin
    2. Lovastatin
  B. Xs sedation
    1. Midazolam
    2. Triazolam
  C. Resp depression
    1. Fentanyl
  D. Tx failure from -> CYP enzymes
    1. Rifampin
    2. St. John’s wart
3. Co-admin w/ caution/dose modification
  A. Warfarin
  B. Sildenafil
  C. Phenytoin
213
Q

PI-enhancing drugs

A 
1. Ritonavir
  A. No longer used alone
  B. Potent CYP3A4 inhibitor, CYP2D6
  C. Low doses inc 2nd PI levels
2. Cobicistat
  A. Inhibits CYP3A4, CYP2D6, and P-gp 
  B. Inc bioavailability atazanavir and darunavir 
    1. Inc serum creatinine -I tubular secretion
214
Q

Integrase inhibitors (INSTIs)

A
  1. Prevent incorporation of HIV DNA into host genome
  2. Often 1st line for newly dx pts
    A. Dec severity of infection
    B. Might -I infection after exposure if given immediately
  3. Agents
    A. Raltegravir
    B. Bictegravir (only coformulation)
    C. Elvietegravir
    D. Dolutegravir
  4. Requires 2 divalent cations
  5. Pregnancy category: X - teratogenic
215
Q 
Integrase inhibitors (INSTIs)
Pharmacokinetics
A
  1. T1/2 = 9hrs w. Cobicistat
  2. Daily dose w/ food
  3. Eliminated they glucuronidase and CYP metabolism
216
Q 
Integrase inhibitors (INSTIs)
ADRs
A 
Generally well tolerated 
1. Common
  A. Nausea
  B. Vomiting
2. Raltegravir (class prototype)
  A. Rhabdomyolysis (rare)
217
Q

Protein synthesis inhibitors

A 
Antibiotics
1. Target bacterial ribosomes
2. Most bacteriostatic
3. Broad spectrum but may narrow w/ evidence
4. Primary challenge: need access to ribosomes
5. Modes of resistance
  A. Antibiotic efflux
  B. Dec uptake
  C. Enzymatic deactivation
218
Q

Steps of bacterial protein synthesis

A
  1. Charged tRNA delivers a.a. To acceptor site on 70S ribosome
    A. Targeted by Tetracyclines and amino-glycosides
  2. Binds growing chain -> peptide bond formation
    A. Macrolides
    B. Clindamycin
    C. Chloramphenicol
  3. Uncharged tRNA released
  4. Chain trans located to peptidyl site
219
Q

Aminoglycosides

A 
Protein synthesis inhibitors 
(ANGST)
1. Amikacin
2. Neomycin (topical)
3. Gentamicin
4. Streptomycin
5. Tobramycin 
6. Broad spectrum
7. Require O2-facilitated transport => anaerobes intrinsically resistant
220
Q

Aminoglycosides MOA

A 
Bind 30S subunit -I initiation protein synthesis -> RNA misreading
  A. Also bacteriocidal
  B. Gram (-) bacilli
    1. E. Coli
    2. Klebsiella pneumonia 
    3. Pseudomonas aeruginosa
221
Q

Aminoglycosides pharmacokinetics

A
  1. Absorption
    A. Low GI
    B. IV, IM (except neomycin-topical)
  2. Distribution variable
    A. CNS: use intrathecal or intraventricular routes
    B. Cross placental barrier and may accumulate in fetal plasma and amniotic fluid
  3. Metabolism/elimination
    A. All t1/2 = 2-3 hrs
    B. >90% excreted unchanged in urine
    C. Bind tissue in kidneys and inner ear -> levels inc 50x than serum
222
Q

Aminoglycosides ADRs

A 
1. Ototoxicity
  A. Vertigo
  B. Deafness
  C. DDIs: other ototoxicity cmpds inc risk
2. Neurotoxicity 
  A. Block release ACh at junction
    1. Weakness and resp depression
    2. Contraindications 
      A. Myasthenia gravis 
      B. Pregnancy
    3. DDIs: neuromuscular jxn blockers
3. Hypersensitivity rxns
  A. Contact dermatitis w/ topical neomycin
223
Q

Tetracyclines

A 
Protein synthesis inhibitor
1. Doxycycline
2. Tigecycline (IV)
  A. 1st one effective against MRSA
3. Minocycline
4. Tetracycline
5. Broad spectrum: best gram (+)
  A. Selective toxicity to bacteria
6. Resistance:
  A. Efflux pathways 
  B. Blocking protein -I tetracycline binding
  C. Enzymatic deactivation
224
Q

Tetracyclines MOA

A

Bind reversible 30S subunit -I tRNA binding mRNA-ribosome complex
1. Drug accumulated in bacteria by transport proteins unique to bacteria

225
Q

Tetracyclines spectrum

A 
1. Against MSSA and MRSA
  A. Peptic ulcer (H. Pylori)
  B. Lyme disease (B. Burgdoferi)
  C. Cholera (vibrio) - doxycycline
  D. Rocky mtn spotted fever (R. Rickettsii)
  E. Atypical species
    1. Mycoplasma pneumonia
  F. Protozoa
  G. Mycobacteria 
  H. Acne
  I. Chlamydia
226
Q

Tetracyclines pharmacokinetics

A 
1. PO (except tigecycline)
  A. Food dec absorption
    1. Except doxycycline and minocycline
  B. Chelate divalent metal ions => don’t take w/ supplements, dairy, and antacids
  C. IM painful => avoid
2. 40-80% bound serum protein
3. Hepatic metabolism
4. Eliminated 
  A. Feces
  B. Urine
5. Can undergo enterohepatic recirculation 
6. Half-life:
  A. Short-acting (T1/2 = 6-8 hrs)
  B. Intermediate (t1/2 =12hrs)
  C. Lon (t1/2 = 16-18 hrs)
227
Q

Tetracyclines ADRs

A 
1. Hypersensitivity uncommon
  A. Photoxicity (25% pts)
2. GI: most common reason to discontinue tx 
  A. Nausea
  B. Vomiting
  C. Diarrhea
3. Slowed bone growth and teeth discoloration
  A. Permanent discoloration if used 4 mo -> 5 y/o
  B. Don’t use <8 y/o or pregnant
4. Hepatotoxicity 
5. Nephrotoxicity 
6. Dizziness 
7. Vertigo
8. Tinnitus
228
Q

Macrolides

A

Protein synthesis inhibitors

  1. Azithromycin (PO, IV)
  2. Clarithromycin (PO)
  3. Erythromycin (PO, IV)
  4. Broad spectrum
  5. Bactericidal at high doses
229
Q

Macrolides MOA

A

Bind 50S subunit -I translocation of growing peptide -> prematurely terming protein synthesis

230
Q

Macrolides spectrum

A 
1. Gram (-) and (+) organisms susceptible to penicillin G
  A. Alternative for people w/ penicillin allergy
  B. Strep pneumonia 
  C. Mycoplasma
  D. Legionnaires disease
  E. Chlamydia infection
  F. Diphtheria 
  G. Pertussis
2. Resistance assoc w/ 
  A. Dec uptake/efflux pump
  B. Dec affinity 50S subunit for Ab gram (+)
  C. Enzymatic degradation gram (-)
3. Erythromycin limited clinical use because inc resistance
  A. Clarithromycin
  B. Azithromycin
  C. Cross resistant
231
Q

Macrolides pharmacokinetics

A
  1. Well absorbed PO
    A. Erythromycin and azithromycin available IV
    B. Food
    1. Dec erythromycin and azithromycin
    2. Inc clarithromycin
  2. Widely distributed (not CSF)
  3. Renal excretion
232
Q

Macrolides ADRs and DDIs

A
  1. GI distress and motility
  2. Hepatotoxicity: cholestatic jaundice
  3. Ototoxicity
    A. Transient deafness (erythromycin)
    B. Irreversible deafness (azithromycin)
  4. Cardiotoxicity: QTc prolongation
  5. Hypersensitivity rxn
  6. DDIs: many w/ other agents competing for CYP450 metabolism
233
Q

Streptogramins

A 
Protein synthesis inhibitors 
1. Usually not first line
2. Quinupristin/dalfopristin (IV)
3. Bactericidal gram (+) cocci, bacteriostatic enterococcus
  A. Usually reserved for severe infections caused by VRE
  B. Atypical pneumonia
4. Resistance mechanism 
  A. Enzymatic deactivation
  B. Efflux pump
234
Q

Streptogramins MOA

A

Bind 50S subunit at separate sites = synergism

  1. Quinupristin -I elongation -> release incomplete peptide chain (similar to macrolides)
  2. Dalfopristin -I elongation by -I adding new a.a. To peptide chain
235
Q

Streptogramins pharmacokinetics

A
  1. Not distributed in CSF

2. Hepatically metabolized and excreted in feces => useful in pts w/ MRSA and renal failure/dysfunction

236
Q

Streptogramins ADRs

A
  1. Phlebitis
  2. Hyperbilirubinemia (25%)
  3. Arthralgia and myalgia (high doses)
  4. Metabolized by CYP3A4 -> DDIs w/ CYP3A4 substrates/inducers
237
Q

Oxazolidinones

A

Protein synthesis inhibitors
1. Linezolid (PO, IV)
2. Binds 23S subunit -I formation of 70S complex
A. Bacteriostatic (except strep - bactericidal)
3. Use
A. Drug-resistant, aerobic, gram (+)
B. Alternate to daptomycin for VRW
4. Resistance: dec binding at target site

238
Q

Oxazolidinones pharmacokinetics

A
  1. Distributes widely
  2. [O] 2 inactive metabolites
  3. Excreted both renal and biliary routes
239
Q

Oxazolidinones ADRs and DDIs

A
  1. GI upset
  2. Nausea
  3. Diarrhea
  4. Headache
  5. Rash
  6. Thrombocytopenia
  7. Neurotoxicity
    A. Irreversible peripheral neuropathy
    B. Optic neuritis -> blindness
  8. DDIs
    A. HTN
    B. Serotonin syndrome w/ lots tyramine-containing foods, selective serotonin reuptake inhibitors, or monoamine oxidase inhibitors
240
Q

Chloramphenicol

A

Protein synthesis inhibitor
1. Broad spectrum: most aerobic and anaerobic bacteria
A. Except pseudomonas
2. Use: life-threatening infections

241
Q

Chloramphenicol MOA

A

Binds 50S subunit -I peptidyl transferase rxn

242
Q

Chloramphenicol pharmacokinetics

A
  1. Well absorbed orally
  2. Penetrates CSF
  3. Inactivated in liver
243
Q

Chloramphenicol ADRs

A
  1. Bone marrow depression and aplastic anemia - usually FATAL
  2. Gray baby syndrome: genetic inability to metabolize
    A. Gray discoloration
    B. Abdominal distention
    C. Vomiting
    D. Flaccidity
    E. Cyanosis
    F. Hypothermia
    G. Dec resp
    H. Vasomotor collapse
244
Q

Lincosamides

A 
Protein synthesis inhibitors
1. Clindamycin (PO, IV, topical)
2. Bacteriostatic gram (+)
3. MOA: binds site on 50S subunit adjeacent macrolides -I adding more a.a. To chain
4. Use: 
  A. MRSA
  B. Strep
  C. Anaerobic bacteria
  D. Good for people w/ beta-lactam allergies
5. Pharmacokinetics 
  A. Nearly 100% orally bioavailable
  B. T1/2 = 3 hrs
6. ADRs
  A. Rash 
  B. SJS (rare)
  C. GI distress
  D. Esp high risk C. Diff
245
Q

DNA/RNA synthesis inhibitors

A

Antibiotics

  1. Indirect: folate antagonists
  2. Direct: quinolones and others
  3. Fluoroquinolones
  4. Folic acid antagonists
  5. Sulfonamides
  6. Cotrimoxazole (TMP-SMZ)
246
Q

Fluoroquinolones

A 
DNA/RNA synthesis inhibitors 
1. Shouldn’t be used 1st line
2. Ciprofloxacin
3. Levofloxacin
4. Moxifloxacin
5. Use
  A. Anthrax
  B. Mycobacterium
  C. Listeria
  D. Chlamydia
  E. UTIs
  F. Resistant resp infections
  G. GI infections
247
Q

Fluoroquinolones MOA

A
  1. Bacterial chromosomes circular and supercool during replication
  2. Bacterial DNA gyrase nicks and seals DNA to combat supercoiling
    A. Drug -I DNA gyrase and topoisomerase -I DNA replication
    B. Only class -I DNA replication
248
Q

Fluoroquinolones pharmacokinetics

A 
1. 90% bioavailability orally
  A. Divalent cations dec absorption
  B. Well distributed 
    1. Bone
    2. CSF
    3. Macrophages
2. Renal elimination
249
Q

Fluoroquinolones ADRs

A 
Well tolerated 
1. Nausea*
2. Vomiting*
3. Headache*
4. Dizziness*
5. Phototoxicity
6. Cardiotoxicity: prolonged QTc
7. Inhibit CYP450-1A2 and 3A4
  A. Theophylline
  B. Tizanidine
  C. Warfarin
  D. Ropinirole
  E. Duloxetine 
  F. Caffeine
  G. Sildenafil
  H. Zolpidem
*leading causes discontinued
250
Q

Folic acid antagonists

A 
DNA/RNA synthesis inhibitors
1. Cotrimoxazole (PO, IV) 
  A. Sulfamethoxazole + trimethoprim
2. Broad spectrum and bacteriostatic
  A. Host cells not affected because have to take in folate
3. MOA: inhibit
  A. Dihydropteroate synthase - sulfonamides
  B. Dihydrofolate reductase - trimethoprim
4. Use
  A. Gram (+) cocci
  B. Gram (-) bacilli
  C. Actinomycetes
  D. Chlamydia
  E. Protozoa
  F. UTIs
251
Q

Sulfonamides

A 
DNA/RNA synthesis inhibitors 
1. Most well absorbed PO
2. Well distributed bound to albumin
  A. CSF
  B. Fetal tissues
3. ADRS
  A. Nephrotoxicity: from crystallization
  B. Hypersensitivity 
    1. Rashes
    2. Angioedema
    3. SJS
  C. Kernicterus: hyperbilirubinemia-assoc brain damage in newborns
     1. Avoid pts <2 m/o, pregnant, breast feeding
252
Q

Cotrimoxazole (TMP-SMZ)

A

DNA/RNA synthesis inhibitors
1. Fixed dose combo trimethoprim-sulfamethoxazole
A. Single or double strength
2. Use
A. Prophylactic and therapy opportunistic infections w/ AIDS
B. UTIs
C. Carriers S. Typhii

253
Q

Polycythemia Vera tx

A
  1. Salicylate
  2. Anticoagulants
  3. Xanthine oxidase inhibitors
  4. Tyrosine kinase inhibitors
  5. Interferon therapy
  6. Antimetabolites
254
Q

Salicylate as PV tx

A
  1. MOA: irreversibly inhibits COX-1 and COX-2 in platelets and -I thromboxane A2 (platelets aggregated)
  2. Pharmacokinetics
    A. T1/2 = 20-30 min aspirin
    B. T1/2 = 6 hrs salicylic acid
  3. Pregnancy category: D in 3rd trimester
  4. Indications
    A. Thrombocytopenia disorder
    B. OA
    C. RA
    D. Fever
    E. Pain
    F. Prophylaxis
    1. Stroke
    2. MI
255
Q

Salicylate ADRs and considerations

A 
1. Common
  A. GI disturbances 
  B. Tinnitus
2. Serious
  A. GI ulcer
  B. Hemorrhage
  C. Reye’s syndrome 
3. Considerations
  A. Allergic rxns
  B. Children and teens Reye’s syndrome
  C. Inhibits aggregation 53% via COX-1
    1. Ibuprofen only 2%
    2. Anti-inflam (COX-2) no platelet effect
256
Q

Anticoagulants

A

Inhibit blood clotting cascade - polycythemia Vera tx

  1. Heparin
  2. Factor Xa inhibitors
  3. Warfarin
257
Q

Heparin

A
  1. High-MW
  2. Enoxaparin (low-MW)
  3. Pregnancy category: C
  4. Indications
    A. Anticoagulant therapy
    B. Thromboembolic disorders
  5. MOA: inc protease action of anti-thrombin II -I thrombin and factor X
  6. Pharmacokinetics
    A. HMW: short t1/2 and unpredictable response
    B. LMW: longer t1/2 and predictable response
258
Q

Heparin ADRs and considerations

A 
Well tolerated
1. Common
  A. Hemorrhage
  B. Bruises easily 
2. Serious
  A. GI hemorrhage
  B. Heparin induced thrombocytopenia (autoimmune activation and platelet destruction)
3. Considerations 
  A. Inc inactivation rxn rate 1000x
  B. Diff heparin have diff anticoag actions 
  C. HMW: effectively catalyzes inactivation of thrombin and factor Xa
  D. LMW: inc inactivation factor Xa
    1. Less effect on thrombin
259
Q

Protamine sulfide

A

Heparin reversal agent

260
Q

Factor Xa inhibitors

A 
Anticoagulant - PV tx 
1. Rivaroxaban (t1/2 = 5-11 hrs)
2. Apixaban (t1/2 = 6-12 hrs)
3. MOA: inhibits Factor Xa
  A. Part of both extrinsic and intrinsic pathways
4. Pregnancy category: C
5. Indications
  A. Tx/prophylaxis DVT
261
Q

Factor Xa inhibitors ADRs and considerations

A 
1. Common
  A. Hemorrhage
  B. Bruise easily 
2. Serious
  A. GI hemorrhage
3. Considerations
  A. Given as fixed dose w/o monitoring
  B. More rapid onset and shorter t1/2 than warfarin
  C. No dietary restrictions
  D. Andexanet alfa (andexxa) = reversal agent
262
Q

Andexanet alfa (andexxa)

A

Factor Xa inhibitor reversal agent

263
Q

Warfarin

A 
Anticoagulant - PV tx 
1. MOA: inhibits liver Vit K reductase
  A. Inhibits regeneration Vit K (essential for clotting factor synthesis in liver)
2. Pharmacokinetics 
  A. T1/2 = 7 days
  B. Metabolized CYP2C9 in liver
  C. Genetic variants in 
    1. CYP2C9: varying rates activity
    2. Vit K epoxied reductase (VKOR): varying response to warfarin
3. Pregnancy category: X
  A. D for pts w/ mechanical heart valve
4. Indications
  A. ITP
  B. Diff types lymphomas and leukemias 
  C. GVHD
264
Q

Warfarin ADRs and considerations

A 
1. Common
  A. Hemorrhage
2. Serious
  A. GI hemorrhage
3. Black box warning: fatal bleeding
  A. Monitor INR
4. Considerations
  A. Reversal agents
    1. Vit K
    2. Fresh frozen plasma
    3. 3/4 factor prothrombin complex concentrate
  B. Avoid aspirin
  C. Monitor PT and INR
  D. Highly protein bound (many DDIs)
  E. CYP metabolized => caution w/ CYP inducers and inhibitors
  F. Avoid Vit K
265
Q

Allopurinol

A 
Xanthine oxidase inhibitors - PV tx
1. t1/2 = 1-2 hrs
2. MOA: dec Uric acid levels by -I xanthine oxidase
3. Pharmacokinetics (PO)
  A. Metabolism: 70% hepatic
    1. Oxypurinol active metabolite
  B. Excretes: 80% kidneys and 20% feces
4. Pregnancy category: B
5. Indications
  A. Inc uric acid levels
  B. Gout
266
Q

Allopurinol ADRs and considerations

A 
1. Common
  A. Pruritus
  B. Rash
  C. GI disturbances
2. Serious
  A. Agranulocytosis
  B. Aplastic anemia
3. Considerations
  A. Concomitant use w/ allopurinol w/ didanosine
267
Q

Ruxolitinib

A 
Tyrosine kinase inhibitor - PV tx 
1. t1/2 = 3 hrs
2. MOA: selectively -I JAK1 and 2
3. Pregnancy category: C
4. Indications
  A. Polycythemia Vera
  B. Myelofibrosis
268
Q

Ruxolitinib ADRs

A 
1. Common
  A. Edema
  B. Bruising
  C. Dizziness
  D. Headache
  E. Anemia
2. Severe
  A. Herpes zoster
  B. Hepatitis
269
Q

Peglylated IFN-alpha

A 
Interferon therapy - PV tx 
1. MOA: enhance host immune system -> inc activated T cells, NK cells, and macrophages
2. Pharmacokinetics 
  A. IFN-a t1/1 = 4-16 hrs
  B. Pegylated t1/2 = 3 days
3. Pregnancy category: C
4. Indications: polycythemia Vera
5. ADRs
  A. Fever
  B. Headache
  C. Chills
  D. Generalized aches and pains
270
Q

Hydroxyurea

A 
Antimetabolite - PV tx 
1. T1/2 = 2-4.5 hrs
2. MOA: inhibits ribonucleotide reductase and -I DNA synthesis
3. Pharmacokinetics 
  A. Renal excretion: 40% unchanged
  B. Liver metabolism: 60%
4. Indications
  A. Sickle cell
  B. Essential thrombocytopenia 
  C. Polycythemia Vera
271
Q

Hydroxyurea ADRs and considerations

A 
1. Common
  A. Nausea
  B. Vomiting
  C. Myelosuppression 
  D. Neutropenia 
  E. Dec platelet count
  F. Dec reticulocyte count
2. Serious
  A. Lower extremity ulcer
  B. Skin cancer
3. Black box warning: severe myelosuppression 
4. Considerations
  A. Dec platelet count
  B. Dec thrombosis risk
272
Q

Primary myelofibrosis (PMF) tx

A
  1. Glucocorticoids

2. Immunomodulators

273
Q

Glucocorticoids

A 
PMF tx 
1. Prednisone
2. Methylprednisolone
3. MOA: dec inflammation
4. Pharmacokinetics 
  A. T1/2 = 2-3.5 hrs
5. Indications: PMF
274
Q

Glucocorticoids ADRs and DDIs

A 
1. Common
  A. Infections
  B. Osteopenia
  C. Osteoporosis 
  D. Adrenal insufficiency avascular necrosis 
  E. Wt Gain
  F. Insomnia
  G. Mood changes
  H. Delirium 
  I. Cataracts
  J. Glaucoma
  K. Striae
  L. Delayed wound healing
2. DDIs
  A. Glucocorticoids + fluoroquinolones-> inc risk tendon rupture
275
Q

Low-dose thalidomide

A 
Immunomodulator - PMF tx 
1. MOA: immunomodulatory and antiangiogenic characteristics
2. Pharmacokinetics 
  A. T1/2 = 5-7 hrs
3. Pregnancy category: X
276
Q

Low-dose thalidomide ADRs

A 
1. Common
  A. Nausea
  B. Vomiting
  C. Fatigue
2. Black box warning: birth defects/embryo fetal death
277
Q

Essential thrombocytopenia (ET) tx

A 
1. Mutations JAK2
  A. 55% JAK2V617F mutation
2. Erythromelalgia
  A. COX-1 inhibitors
  B. If doesn’t respond
    1. Hydroxyurea 
    2. Pegylated IFN-a
    3. Anagrelide
3. Platelet reducing agents
278
Q

Anagrelide

A 
Platelet reducing agent - ET tx 
1. MOA: inhibits PDE-3 -I platelet aggregation and dec platelet production
2. Pharmacokinetics 
  A. T1/2 = 1.3-1.7 hrs
  B. Daily dose
3. Pregnancy category: C
4. Indications
  A. Thrombocytosis 
  B. Secondary to myeloproliferative disorders
279
Q

Anagrelide ADRs and considerations

A 
1. Common
  A. Headache
  B. Edema
  C. Diarrhea
  D. Heart palpitations
2. Serious 
  A. Prolonged QT interval
  B. Hemorrhage 
3. Considerations
  A. Pts report CV symptoms
280
Q

Acute lymphoblastic leukemia (ALL) tx

A 
1. Goal: complete remission
  A. <5% blasts 
  B. Normal hematopoiesis
  C. Cured if NED 5 yrs
2. Childhood remission 96-99%
3. Adult remission 30-40%
4. Tx phases (2-3 yrs)
  A. Induction 
  B.CNS prophylaxis
  C. Consolidation therapy 
  D. Delayed intensification 
  E. Interim maintenance 
  F. Maintenance therapy
5. Anthracyclines 
6. Mitoxantrone
7. Imatinib 
8. Methotrexate
9. Purine antagonists
10. Cyclophosphamide and ifosfamide
281
Q

Anthracyclines

A 
Chemotherapy (ALL)
1. Agents
  A. Doxorubicin
  B. Daunorubicin
  C. Idarubicin
  D. Epirubicin
  E. Valrubicin
2. Red color
282
Q

Anthracyclines MOA

A
  1. Intercalate into DNA
  2. Topoisomerase II inhibitor
  3. Generate semiquinone free radicals and O2 free radicals
    A. Cause cardiotoxicity via Fenton pathway because cardiac tissue lacks catalase
283
Q

Anthracycline ADRs

A
  1. Vesicants
  2. Irreversible CHF
    A. Chemoprotective agent
    1. Dexrazoxane - iron chelator
      B. Agents have life-time limits
      C. Acute cardiotoxicity
    2. Arrhythmias
    3. Conduction abnormalities
      D. Chronic cardiotoxicity
    4. Dose-dependent
  3. Mucositis
  4. Stomatitis
284
Q

Mitoxantrone

A

Chemotherapy - synthetic anthracycline (ALL)
1. Blue/green color
2. MOA: intercalation -I topoisomerase II -> strand breakage and cell death
A. No free radicals
3. ADR: mucositis

285
Q

Imatinib

A

Chemotherapy (ALL) - tyrosine kinase inhibitor
1. Targets
A. BCR-ABL
B. KIT receptor
C. Platelet-derived growth factor receptor (PDGFR)
2. MOA: inhibit proliferation -> apoptosis
3. Indications
A. CML
B. GIST
C. Ph+ ALL

286
Q

Imatinib ADRs

A
  1. Nausea
  2. Vomiting
  3. Edema
  4. Arthralgia/myalgia
  5. Myelosuppression
287
Q

Methotrexate (MTX)

A 
Chemotherapy (ALL)
1. MOA: inhibits dihydrofolate reductase (DHFR) -I folate reduction -I DNA synthesis
  A. Indirect -I thymidylate synthase
2. ADRs
  A. Mucositis
  B. Photosensitivity
  C. Nephrotoxicity 
3. Leucovorin = rescue agent
288
Q

Leucovorin

A

Rescue agent for methotrexate

289
Q

Purine antagonists

A 
Chemotherapy (ALL)
1. Agents
  A. 6-mercaptopurine
  B. 6-thoiguanine
2. MOA: inhibit biosynthesis AMP and GMP
3. Pharmacokinetics 
  A. Metabolized thiopurine methyl transferase (TPMT)
     1. Poor metabolized -> build up -> toxicity => dec dose
290
Q

Purine antagonists ADRs

A
  1. 6-mercaptopurine
    A. Hepatotoxicity (inc liver enzymes)
  2. 6-thioguanine
    A. Mostly just common ADRs
291
Q

Cyclophosphamide and ifosfamide

A 
Chemotherapy (ALL)
1. Pro drugs -> aziridinium ion
2. Form acrolein-> builds up in bladder -> hemorrhagic cystitis
  A. -SH group of cysteine in bladder alkylated 
  B. Severe hemorrhage
  C. Sclerosis
  D. Possible bladder cancer
3. Min acrolein affects
  A. Hydration
  B. Mesna
292
Q

Mesna

A

Chemoprotective agent for cyclophosphamide and ifosfamide

293
Q

Acute myeloid leukemia (AML) tx

A 
1. Goal: complete remission
  A. <5% blasts 
  B. Normal hematopoiesis
2. Tx phases (2-3 yrs)
  A. Induction 
  B.CNS prophylaxis
  C. Consolidation therapy 
  D. Delayed intensification 
  E. Interim maintenance 
  F. Maintenance therapy
3. DNA polymerase and chain elongation inhibitors
294
Q

Cytarabine and Gemcitabine

A

Chemotherapy (AML) - DNA polymerase and chain elongation inhibitors
1. Cytidine analogs
2. Metabolized -> active false substrate
A. Compete w/ cytidine for DNA polymerase
B. Incorporated into DNA -> chain termination and cell death
C. Inhibits DNA repair enzymes and RNA synthesis
3. High cellular specificity for lymphoid cells

295
Q

Cytarabine and Gemcitabine ADRs

A
  1. Hand and foot syndrome

2. Rash

296
Q

Halogenated adenosine analogs

A
  1. Agents
    A. Fludarabine
    B. Cladribine
    C. Clofarabine
  2. Metabolized -> active false substrate
    A. Compete w/ adenosine for DNA polymerase
    B. Incorporated into DNA -> chain termination and cell death
    C. Inhibits DNA repair enzymes and RNA synthesis
297
Q

Halogenated adenosine analogs ADRs

A
  1. Fludarabine: cough

2. Cladribine: stomatitis

298
Q

Chronic lymphocytic leukemia (CLL) tx

A
  1. Goal: remission
  2. Alkylating agents
  3. Rituximab
299
Q

Alkylating agents

A 
Chemotherapy (CLL) - alkylating agents
1. Nitrogen mustards
2. MOA: bifunctional
  A. Act as strong electrophile to destabilize DNA -I synthesis
  B. Cross-link DNA
3. Mechlorethamine (IV)
300
Q

Alkylating agents ADRs

A
  1. Mechlorethamine
    A. Powerful vesicant
  2. Extravasation
301
Q

2% sodium thiosulfate

A

Nitrogen mustard chemoprotective agent

  1. Strong nuc-
  2. Creates H2O soluble cmpd for elimination
302
Q

RItuximab

A

Chemotherapy (CLL)
1. Chimeric Ab
2. MOA: targets CD20 on normal and malignant cells
A. Recruit immune effector fxns -> B cell lysis
3. Indications
A. NHL
B. CLL

303
Q

RItuximab ADR

A

SJS

304
Q

Chronic myelogenous leukemia (CML) tx

A
  1. Dasatinib

2. Nilotinib

305
Q

Dasatinib

A 
Chemotherapy (CML)
1. Multi-tyrosine kinase inhibitor targeting
  A. SCR TK
  B. PDGFR
  C. BCR-ABL
  D. C-KIT kinase
2. Active against imatinib-resistant leukemia
3. Applications
  A. Ph+ CML
  B. Ph+ ALL
306
Q

Dasatinib ADRs

A
  1. Edema and pleural effusion

2. Hemorrhage

307
Q

Nilotinib

A

Chemotherapy (CML) - BCR-ABL TK inhibitor
1. Higher affinity BCR-ABL than imatinib and dasatinib
2. Used Ph+ CML
3. Competitive inhibitor
4. Inhibits proliferation and -> apoptosis
5. Applications
A. Ph+ CML
B. Imatinib-resistant Ph+ CML

308
Q

Nilotinib ADRs

A

Electrolyte abnormalities

309
Q

Hodgkin lymphoma tx

A 
1. Protocols
  A. ABVD
  B. Stanford V
2. Anti tumor antibiotics 
3. Brentuximab vedotin
4. Topoisomerase inhibitors
5. Vinca alkaloids
6. Toxanes
310
Q

Bleomycin

A 
Chemotherapy (HL) - antitumor antiboitic
1. Active in G2 phase
2. MOA: binds DNA and chelates Fe3+ -> free radical -> single and double-strand DNA breaks
3. Bleomycin hydrolase -I action
4. Given
  A. SQ
  B. IM
  C. IV
5. Renal excretion
311
Q

Bleomycin ADRs

A

Pulmonary fibrosis

312
Q

Brentuximab vedotin

A

Chemotherapy (HL) - anti CD30+ Ab conjugated to MMAE
1. CD30: tumor necrosis factor
A. Reg proliferation and differentiation of lymphocytes
B. Only on activated B and T cells in healthy tissue
C. HL (> or = 95%) and anaplastic large cell lymphoma
2. 3 components
A. Chimeric Ab
B. Drug
1. MMAE
2. Inhibits microtubule polymerization
C. Protease-cleavage linker
3. Application
A. HL
B. Anaplastic large cell lymphoma

313
Q

Brentuximab vedotin MOA

A
  1. Target CD30 on HL and ALCL
  2. Linker cleaved by proteases -> release MMEA
  3. MMEA -I tubulin polymerization
314
Q

Brentuximab vedotin ADRs

A
  1. Neutropenia
  2. Peripheral sensory neuropathy
  3. Fatigue
  4. Nausea, vomiting, diarrhea
  5. Anemia
  6. Upper resp tract infection
  7. Black box warning: progressive multifocal leukoencephalopathy (PML)
315
Q

Topoisomerase I inhibitors

A 
Chemotherapy (HL)
1. Single strand breaks
2. Stabilize DNA strand break and -I TI from religating the break
3. Camptothecins
  A. Irinotecan
  B. Topotecan
316
Q

Topoisomerase II inhibitors

A 
Chemotherapy (HL)
1. Double strand breaks
2. Stabilize DNA strand break and -I TI from religating the break
3. Epipodophyllotoxins
  A. Etopooside
  B. Teniposide
317
Q

Epipodophyllotoxins ADR

A

Mucositis

318
Q

Vinca alkaloids

A 
Chemotherapy (HL)
1. MOA: inhibit microtubule polymerization 
  A. Bind beta-tubulin
  B. Inhibit assembly microtubules 
  C. No mitotic spindle
  D. Mitotic arrest
  E. Apoptosis
2. Agents
  A. Vincristine
  B. Vinblastine 
  C. Vinorelbine (long t1/2)
319
Q

Vinca alkaloids ADRs

A
  1. Alopecia

2. Neurotoxicity

320
Q

Toxanes

A 
Chemotherapy (HL)
1. MOA: inc microtubule formation by -I disassembly of tubulin
  A. Bind beta-tubulin -> dec depolymerization 
  B. Cell arrest in mitosis
2. Agents
  A. Paclitaxel
  B. Docetaxel
  C. Cabazitaxel
321
Q

Toxanes ADRs

A
  1. Alopecia

2. Peripheral neuropathy

322
Q

Bendamustine

A 
Chemotherapy (NHL)
1. N-methylbenzimidazole analog of chlorambucil
2. Purine-like ring
3. Dual MOA:
  A. Alkylation of DNA -> extensive and less repairable DNA damage
  B. Antimetabolite mechanism
    1. S phase
    2. “Mitotic catastrophe”
    3. Apoptosis
323
Q

Bendamustine ADRs

A

Inc bilirubin levels

324
Q

5th generation cephalosporin mnemonic

A
  • ro and -lo
    1. CeftobipROle
    2. CeftaROline
    3. CefttoLOzane
325
Q

4th generation cephalosporin mnemonic

A
  • pi- and -qui-
    1. CefaPIme
    2. CefQUInome
326
Q

2nd generation cephalosporin mnemonic

A

FURy FOX FOR FON TEA and 2 Ms for a Macho fox

  1. CeFURoxime
  2. ceFOXitine
  3. CeFORanide
  4. CeFONicid
  5. CefoTEtan
  6. CefMandole
  7. CefMetazole
  8. Cefaclor
327
Q

1st generation cephalosporin mnemonic

A 
2Xs and 1z IN Dine
A after cef (except cefaclor -2nd)
1. 2X
  A. CefaleXin
  B. CefadroXil
2. 1Z
  A. CefaZolin
3. 2 IN
  A. CefalothIN
  B. CefaparIN
4. DINE
  A. Cephradine

BIIC (7 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions