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Block F: Immunnology > Fever et 1stweek pharma > Flashcards

Fever et 1stweek pharma Flashcards

1
Q

Acute lymphoblastic leukemia: go-to drugs? (3)

A
  • Vincristine
  • Prednisone
  • Doxorubicin/Daunorubicin
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2
Q

What are the leukemia/lymphoma drugs targeting steroid hormone receptors?

A

 Glucocorticoid: prednisone

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3
Q

What is aspirin overdose?

A

Aspirin overdose: combined metabolic acidosis and respiratory alkalosis

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4
Q

Therapeutic uses of antihistamines? (3)

A
  • Allergic reactions: allergic rhinitis, atopic dermatitis, hay fever
  • Motion sickness
  • Sedation and hypnotics for sleep-aids
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5
Q

What does Vincristine and Vinblastine do?

A

Bind to tubulin, terminate assembly, cause depolymerization of microtubules and mitotic arrest

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6
Q

Hodgkin lymphomas go-to drugs? (4)

A
  • Doxorubicin (Adriamycin)
  • Bleomycin
  • Vinblastine
  • Dacarbazine
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7
Q

The Histamine H1 receptor is involved in what? (2)

A

H1 (Gq-coupled to phospholipase C (PLC)): involved in bronchoconstriction, vasodilation allergic rhinitis. Antihistamines are H1 receptors antagonists

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8
Q

IL-1 and TNF-a do what with respect to fever?

A

IL-1 and TNF-a stimulate the production of IL-6. They go to the anterior hypothalamus and stimulate increase of prostaglandins PGE2 (which is not involved in normal thermoregulation)

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9
Q

Advantages of fever? (4)

A
  • Some bacteria and viruses grow slowly at temperature over 40
  • Decrease the availability of iron, required by bacteria for growth
  • Neutrophils kill more easily at high temp
  • Activated dendritic cells move more quickly to the regional lymph nodes
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10
Q

Non-Hodgkin lymphomas go-to drugs? (4)

A
  • Cyclophosphamide
  • Doxorubicin
  • Vincristine
  • Prednisone
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11
Q

Second generation antihistamines: used for what?

A

Allergies

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12
Q

Stats of severe/febrile neutropenia?

A
  • Severe/Febrile: <500What cells/uL
    o Absolute number of neutrophils in febrile neutropenia: 0.5
  • Profound: <100 cells/uL
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13
Q

Three characteristics of NSAIDS (ibuprofen)?

A

Anti-analgesia, antipyretics, anti-inflammatory

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14
Q

What are the leukemia/lymphoma drugs targeting microtubules? (3)

A

 Vincristine
 Vinblastine
 Taxols

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15
Q

NSAIDS and pregnancy?

A

Don’t give NSAIDs to pregnant women: it closes ductus

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16
Q

First generation antihistamines include the following: (4)

A

o Diphenhydramine (Benadryl): used for motion sickness
o Chlorpheniramine
o Promethazine
o Cyclizine

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17
Q

Second generation antihistamines includes what?

A
  • Cetirizine (Zyrtec)
  • Fexofenadine (Allegra): don’t take grapefruit juice, this can cause Torsade de pointes and delayed polarization via the HERG expression channel
  • Loratadine (Claritin)
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18
Q

What does Methotrexate and 5-Fluorouracil do?

A

 Methotrexate: folic acid analog that targets dihydrofolate reductase and prevents it to make thymidylate (DNA building block) from thymidylate synthase
 5-Fluorouracil: also prevents the thymidylate synthase construction block of DNA

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19
Q

What are the leukemia/lymphoma drugs targeting enzymes involved in cell signaling? What does it do?

A

 Tyrosine kinase inhibitor (imatinib): inhibits a cancer specific tyrosine kinase formed by a translocation

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20
Q

What does Cytarabine do?

A

 Cytarabine: competes to be included in the DNA, but will triggers apoptosis following a strand break

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21
Q

Causes/pathogenesis of febrile neutropenia? (7)

A
  • Mucositis: chemo/radiation breaks the mucosal integrity, causing lesions. This causes majority of neutropenic fevers
  • Tumors themselves can cause obstruction of urinary, GI, respiratory, biliary tracts or lymphatics
  • Biopsy and intravenous lines abrogate skin barrier
  • Impaired neutrophil function: chemotaxis
  • Neutropenia due to myelosuppression (chemo/radiation)
  • Impaired humoral immunity via impaired antibody production (myeloma, chronic lymphocytic leukemia, splenectomy)
  • Impaired cell immunity in case of lymphoma, glucocorticoids, HIV
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22
Q

What are the leukemia/lymphoma drugs targeting antibodies? (3)

A

 Anti-CD20 (Rituximab)
 Anti-CD30 (Brentuximab vedotin)
 Anti-PD1 (Pembrolizumab)

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23
Q

What are enndogenous pyrogens?

A

Protein producing fever

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24
Q

What are the leukemia/lymphoma drugs targeting DNA Alkylation? (2)

A

o DNA Alkylation: destroy rapidly dividing cells (not only cancer cells, but also hematopoietic system, GI tract and gonads). Resistance to those drugs may be due to increased inactivation, increased DNA repair and decreased activation
 Cyclophosphamide: N7 position crosslink the DNA, preventing damage repair
 Dacarbazine

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25
What is febrile neutropenia?
Fever in neutropenic patient (most often patients on chemo) is a medical emergency Symptoms: - Frequent infections - Unexplained fever
26
What is a febrile neutropenia high-risk patient ?
High risk: neutropenia count <100 neuts/uL for >7days
27
IgE-Antibody induced release (things that provoke the release of histamines)? (3)
Food, penicillin, venoms, etc
28
What does Anti-CD20 (Rituximab) do?
Destroys both normal and malignant B-cells (good for B-cell non-Hodgkin lymphomas that are CD20+ and chronic lymphocytic leukemia CLL)
29
Adverse effects of aspirin and NSAIDs?
Due to loss of prostaglandin cytoprotective action (decrease in protective mucus and mucosal blood flow): - Gastrointestinal bleeding (ulceration) - Renal failure
30
S phase specific leukemia/lymphoma drugs? (3)
Anti-metabolites:  Methotrexate  5-Fluorouracil  Cytarabine
31
What are the four most common etiologies of febrile neutropenia?
- Gram positive is most common (staph epidermis is most common in gram positive) - Gram negative - Invasive fungi: Candida and Aspergillus are most common - Viruses: HSV 1, HSV 2 (herpes), HZV “shingles”, respiratory viruses
32
When there’s brain injury, fever can do what?
When there’s brain injury, fever can exacerbate the injury via increased toxic neurotransmitter release, increased oxygen free radical production and disruption of blood-brain barrier
33
Why does NSAIDs cause renal failure?
- Renal failure: NSAIDs (ibuprofen) block the Na, K and water excretion and may cause increased blood pressure
34
Signs of NSAID sensitity? (5) What explains NSAID sensitivity and what should you do?
``` - NSAID sensitivity: if you see this, avoid salicylates/NSAIDs and go for acetaminophen instead. This is due to inhibition of the Cyclooxygenase pathway o Rhinitis o Nasal polyps o Asthma o Laryngeal edema o Bronchospasm ```
35
Temperatures of hyperthermia and hyperpyrexia?
- Hyperthermia: between 38.5 and 41.5 degree | - Hyperpyrexia: >41.5
36
What are the leukemia/lymphoma drugs targeting Topoisomerase inhibitors? (2)
 Daunorubicin/Doxorubicin |  Bleomycin (DNA damage)
37
What does Anti-CD30 (Brentuximab vedotin) do?
Conjugated via a protease-cleavable linker to a potent anti-microtubule agent
38
Chronic myelogenous leukemia go to drug?
Imatinib
39
Strict and usual definitions of neutropenia in terms of stats?
- Strict def: <1800 cells/uL | - Usual def: <1500 cells/uL
40
What is the mechanism of histamine release?
Most important mechanism of histamine release is immunological stimulus. Mast cells degranulate if surface IgE is stimulated (or if mast cell is destroyed), and this release histamines. This is seen in (type I) allergic reaction
41
What is the treatment for low risk febrile neutropenia? (2)
Fluoroquinoline and Beta-Lactam, then discharge if they live close to the hospital
42
Absolute neutrophil count: ?
Absolute neutrophil count: ANC = total wbc count x %(neutrophils + bands)
43
What does Cyclophosphamide do?
N7 position crosslink the DNA, preventing damage repair
44
Effects of both aspirin and NSAIDs: (2)
o Anti-pyretic action by blocking the production of PGE2 to reset the hypothalamic temperature set point o Anti-platelet/anti-thrombotic: decreases platelet production of TXA2 by binding irreversibly to COX-1 to limit platelet aggregation and vasoconstriction
45
What does Daunorubicin/Doxorubicin do?
Intercalate in DNA, and inhibit topoisomerase II, which cause a DNA strand break
46
What are the important Toll-Like receptors (TLR) for fever? (3)
IL-1, IL-6 and TNF-a
47
Cell cycle non specific leukemia/lymphoma drugs (3)
 Cyclophosphamide  Dacarbazine  Bleomycin
48
What regulates temperature?
Core temperature is regulated by the hypothalamus, so fever is change of hypothalamus set point
49
What does acetminophen do? Three characteristics?
- Acetaminophen: analgesic and anti-pyretic via inhibition of neuronal and vascular PGE2 generation o Weak anti-inflammatory, little GI toxicity and anti-platelet activity
50
What are the leukemia/lymphoma drugs targeting anti-metabolites? (3)
 Methotrexate  5-Fluorouracil  Cytarabine
51
Normal temperatures
Normal temperature ranges from 35.6 to 38.5 +0.6 degrees higher after ovulation. Lowest at 6am, highest at 4-6pm
52
What is an autacoid? What medications are autocoids? (5)
Autacoids: something locally released that is short-duration. This includes: - Histamine - Serotonin - Endogenous peptides - Prostaglandins - Leukotrienes
53
Side effects of first generation antihistamines? (8)
``` o Sedation o Dizziness o Peripheral anti-muscarinic effects:  Dry mouth  Blurred vision  Constipation  Urinary retention o Potentiate CNS depressants (opioids, sedatives, narcotics, alcohol) o Can cross the placenta ```
54
Causes of fever? (7)
- Infections - Rheumatic diseases/autoimmune - Tissue damage/trauma - Malignancies - Endocrine/Thyrotoxicosis - Immune reactions - Autoinflammatory diseases
55
What are exogenous pyrogens?
Bacterial products causing fever
56
Disadvantages of fever? (3)
- Increased CO2 production - Water loss - Cerebral injury (like febrile seizures)
57
Histamine can cause what? (5)
Histamine can cause: acute inflammatory reaction - Allergies - Asthma - Anaphylaxis - Duodenal ulcers - Zollinger-Ellison Syndrome
58
What does Anti-PD1 (Pembrolizumab) do?
Allows T-cells to kill tumor cell in Hodgkin lymphoma
59
Variation of temperature measurement when taken orally?
- Oral temperature about 0.6 degrees lower
60
Three characteristics of Aspirin?
Anti-analgesia, antipyretics, anti-inflammatory
61
What does Bleomycin do?
Binds to DNA and iron to form free radicals in order to cause DNA strand break
62
Symptoms of histamine release? (6)
- Itching, redness - Skin reactions - Tachycardia - Mild respiratory distress - Anaphylaxis: o Severe hypotension, ventricular fibrillations, cardiac arrest
63
Fexofenadine (Allegra): don’t take grapefruit juice with it because...?
- Fexofenadine (Allegra): don’t take grapefruit juice, this can cause Torsade de pointes and delayed polarization via the HERG expression channel
64
M phase specific leukemia/lymphoma drugs? (3)
Microtubules:  Vincristine  Vinblastine  Taxols
65
Hepatotoxicity occurs with ingestion of how much acetaminophen?
o Hepatotoxicity when dose >4gm/day or less with binge drinking
66
What is the treatment for high risk febrile neutropenia? (6 elements)
 Start with IV antibiotics  Initiate monotherapy with anti-pseudomonal Beta-lactam antibiotics (Meropenem or Piperacillin-Tazobactam)  Don’t cover gram positive from the start, since they are rarer. If you discover gram positive, go for Vancomycin  If nothing works, suspect fungus infection. Go for Caspofungin (for Candida) or Voriconazole (for Aspergillus)  Remove catheter  Maintain treatment until they recover >500neuts/uL and is afebrile for 48h

Block F: Immunnology (9 decks)

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