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PT 1 > L46-48 Pulm > Flashcards

L46-48 Pulm Flashcards

1
Q

What are the two categories of asthma?

A
  1. Intermittent

2. Persistent

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2
Q

What is the medication of choice for the treatment of bronchospasm?

A

Beta-2 adrenergic agonists (bronchodilators)

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3
Q

What are the selective short-acting beta 2-adrenergic agonists used for asthma?

A
  1. Albuterol
  2. Terbutaline
  3. Metaproterenol
  4. Bitolterol
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4
Q

What are the long-acting beta 2-adrenergic agonists used for asthma?

A
  1. Salmeterol
  2. Formoterol
  3. Vilanterol
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5
Q

What is the MoA of beta-2 agonists?

A

Stimulates adenylyl cyclase, increases cAMP in smooth muscle, leading to powerful bronchodilation

Inhibits release of mediators from mast cells

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6
Q

How are bronchodilators administered?

A
  1. Metered inhaler (faster, more potent, fewer side effects)
  2. Nebulizer (expensive, contamination, more consistent)
  3. Oral (slower, more side effects)
  4. Parenteral
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7
Q

What are side effects of bronchodilators?

A
  1. Skeletal muscle tremors
  2. Tachycardia
  3. Anxiety/restlessness/apprehension
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8
Q

Theophylline is a methylxanthine that inhibits phosphodiesterase and is a competitive antagonist for adenosine receptors. Why is it rarely used?

A

Frequent side effects (convulsions, tachycardia), drug interactions, limited effectiveness, risk of life-threatening complications from OD, narrow therapeutic window

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9
Q

What are the two muscarinic antagonists used to treat asthma? When are they used?

A
  1. Ipratropium
  2. Tiotropium

Patients who can’t tolerate beta 2 agonists

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10
Q

What is the MOA of muscarinic antagonists?

A

Competitively blocks muscarinic receptors in the airway, inhibit ACh, prevents bronchoconstriction

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11
Q

The side effects of muscarinic antagonists are minimal, but they can have ___-like effects at high dosages.

A

Atropine

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12
Q

What are the inhaled corticosteroids used to treat asthma?

A
  1. Beclomethasone
  2. Flunisolide
  3. Fluticasone
  4. Momentasone
  5. Triamcinolone
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13
Q

What is the oral corticosteroid used to treat asthma?

A

Prednisone

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14
Q

What is the IV corticosteroid used to treat asthma?

A

Methylprednisolone

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15
Q

What is the MOA of inhaled corticosteroids?

A

Reduce the synthesis of arachidonic acid by inhibiting phopholipase A2 activity; this inhibits the synthesis and release of leuktrienes and prostaglandins

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16
Q

How are inhaled corticosteroids used to treat asthma?

A

First line prophylactic therapy for persistent asthma

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17
Q

What are short-term side effects of oral corticosteroids?

A

Increased energy, insomnia, hunger, agitation, mood alteration

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18
Q

What are long-term side effects of oral corticosteroids?

A

Osteoporosis, cataracts, myopathy, HPA axis suppression, depression

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19
Q

What are side effects of inhaled corticosteroids?

A

Oropharyngeal candidiasis, vocal cord changes, nose bleeds, mucosal irritation

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20
Q

What is the MOA of Cromolyn and when is it used?

A

Decreases the release of histamine and leukotrienes; prevent symptoms before exposure to a trigger (exercise and cold asthma), alternative to low dose glucocorticoids - less effective, nebulizer, must be used 3-4x/day

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21
Q

What are the leukotriene antagonists?

A
  1. Montelukast
  2. Zafirlukast
  3. Zileuton
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22
Q

What is the MOA of the leukotriene antagonists?

A

Montelukast and zafirlukast are LT receptor antagonists. Zileuton is an inhibitor of 5-lipoxygenase. They all open narrowed airways, decrease inflammation and mucus production.

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23
Q

What are the side effects of leukotriene antagonists?

A

Mood alterations, depression, headache, nausea

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24
Q

When is Zileuton contraindicated?

A

Hepatic disease

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25
Q

What is Omalizumab and what is its MOA?

A

Monoclonal Ab to human IgE

Forms a complex with free IgE to lower serum levels; prevents IgE from binding to mast cells and releasing histamine and leuktorienes

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26
Q

Which treatment is used for symptom relief of bronchospasm in acute asthma attacks?

A

Short and long acting beta-2 agonists

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27
Q

___ is used in combination with corticosteroids in an inhaler for persistent asthma.

A

SABA/LABA

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28
Q

Which treatments are used as maintenance therapy for chronic asthma?

A
  1. Theophylline

2. Corticosteroids

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29
Q

What is unique about Theophylline?

A

Sustained release oral therapy

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30
Q

Which treatment is used alone or in combination with beta-2 adrenergic agonists in acute asthma?

A

Muscarinic antagonists

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31
Q

Which treatments are used prophylactically to prevent bronchospasm?

A
  1. Cromolyn

2. Leukotriene inhibitors

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32
Q

What are the side effects of Cromolyn?

A

Occasional coughing

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33
Q

How are allergies treated in young children?

A
  1. Comolyn sodium (nasal spray)

2. Second generation anti-histamines

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34
Q

What are the second generation anti-histamines?

A

Loratadine, Certirizine, Fexofenadine

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35
Q

Why should first generation anti-histamines be avoided in young children?

A

Sedative effects

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36
Q

How are allergies treated in older children and adults with mild symptoms?

A
  1. Second generation oral antihistamine
  2. Antihistamine nasal spray
  3. Glucocorticoid nasal spray
  4. Cromolyn nasal spray
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37
Q

What are the anti-histamine nasal sprays?

A

Azelastine, Olopatadine

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38
Q

What are the glucocorticoid nasal sprays?

A

1st generation (10-50% bioavailability) - beclomethasone, flunisolide

2nd generation (<2% bioavailability) - mometasone, fluticasone, ciclesonide

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39
Q

How are allergies treated in older children and adults with moderate to severe symptoms?

A

Glucocorticoid nasal sprays (most effecitve)

Failure to respond adequately - add a second agent

Concomitant asthma - add montelukast

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40
Q

Which agent is most effective for relief of nasal symptoms?

A

Glucocorticoid nasal sprays > oral antihistamines

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41
Q

What is the MOA of glucocorticoid nasal spray?

A

Down-regulate inflammation by inhibiting phospholipase A2

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42
Q

What are the side effects of glucocorticoid nasal sprays?

A

Nose bleeds, irritation of nasal mucosa

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43
Q

What are the drug interactions of glucocorticoid nasal sprays?

A

Fluticasone and strong inhibitors of CYP3A4 (ritonavir, itraconazole)

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44
Q

Why do first generation anti-histamines cause significant sedation?

A

Lipophilic and cross the blood brain barrier

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45
Q

What side effect are second generation anti-histamines associated with?

A

Weight gain

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46
Q

___ may decrease the effects of loratadine and fexofandine.

A

St. John’s Wort

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47
Q

What is the MOA of anti-histamines?

A

Block the binding of histamine to its receptor, reduced release of histamine and other mediators

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48
Q

What provides better symptom relief than antihistamines alone?

A

Oral antihistamine + decongestant

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49
Q

What are the side effects of decongestants?

A

HTN, insomnia, irritability, headache

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50
Q

What is the main first generation antihistamine?

A

Diphenhydramine (Benadryl)

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51
Q

What is the main second generation antihistamines?

A

Fexofenadine (Allegra), loratidine (Claritin), cetirizine (Zyrtec)

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52
Q

Broadly, what three things are immunosuppressant drugs used for?

A
  1. Prevent rejection of transplantation
  2. Treat autoimmunity
  3. Prevent host vs. graft/graft vs. host disease
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53
Q

What are the classes of immunosuppressant/immunoregulatory drugs?

A
  1. Ab for induction immunosuppression
  2. Glucocorticoids/steroids
  3. Proliferation inhibitors and anti-metabolites
  4. Immunophilin-binding drugs (inhibitors of T-cell signaling pathways)
  5. Immune checkpoint inhibitors
  6. Miscellaneous drugs used to treat relapsing-remitting MS
  7. Passive immunization Ig
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54
Q

Immunosuppressive therapy is aimed at preventing ___ rejection and prolonging graft survival.

A

Acute

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55
Q

What are the 4 general principles of transplantation and immunosuppressive therapy?

A
  1. Appropriate patient and donor preparation and selection (blood type, HLA-match)
  2. Multi-tiered approach to immunosuppression
  3. Potent initial immunosuppression (allows for lower doses of maintenance therapy)
  4. Reduce or withdraw drugs if toxicity > benefits
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56
Q

What are the general risks of immunosuppression?

A

Increased risk of infection and malignancy, post-transplant lymphoproliferative disorder

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57
Q

What are the two components of immunosuppressive therapy of organ transplant recipients?

A
  1. Induction therapy (intraoperatively and 3-7 days post-transplant)
  2. Maintenance immunotherapy (triple drug regiment post-op)
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58
Q

What are the components of the triple drug regimen used in maintenance immunotherapy?

A
  1. Glucocorticoid
  2. Cyclosporin or Tacrolimus
  3. Anti-proliferative drug

*Sirolimus/everolimus can replace #2 or #3

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59
Q

What is induction therapy?

A

Use of anti-lymphocyte Ab to acutely inhibit T-cell responses in the recipient at the time of transplantation

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60
Q

What are the two types of anti-lymphocyte antibodies used in induction therapy?

A
  1. Lymphocyte depleting

2. Functional inhibition

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61
Q

What are the 3 Ab induction reagents?

A
  1. Rabbit anti-thymocyte globulins (rATG)
  2. Alemtuzumab
  3. Basiliximab
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62
Q

How does rATG work?

A

Reacts with proteins expressed on lymphocyte surface (CD 2, 3, 4, 8, 11a), actively depletes lympohcytes from the blood and lymphoid organs

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63
Q

How does Alemtuzumab work?

A

Anti-CD52, actively depletes T cells by triggering Ab-mediated lymphocyte lysis

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64
Q

How does Basiliximab work?

A

Humanized Ab that binds CD25 (alpha-chain of IL-2R), inhibits T-cell proliferation (less effective than depleting Ab)

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65
Q

Generally, what are the adverse effects of the antibody induction reagents?

A

Cytokine release syndrome, prolonged leukopenia, increased infections

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66
Q

Which Ab induction reagent is well-tolerated but has more rejection than other agents?

A

Basiliximab

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67
Q

What are the key glucocorticoids?

A

Prednisone (pro-drug), Prenisolone (active)

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68
Q

What do steroids do?

A

Inhibit immune system, inhibit expression of pro-inflammatory genes, decrease # of circulating leukocytes

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69
Q

What is the MOA of glucocorticoids?

A

Diffuse into cells, bind their receptors in cytoplasm, promote receptor dimerization, nuclear translocation, active receptors bind to target genes and inhibit critical immunoregulatory genes

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70
Q

In addition to prevention of organ graft rejection, what else can steroids be used for?

A

High dose IV pulses: acute rejection episodes, GvHD in BMT, treatment of cytokine-release syndrome

Autoimmune/inflammatory disease: RA, SLE, MS, psoriasis, IBD, skin diseases, eye diseases, asthma, etc.

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71
Q

What are some of the serious AE associated with chronic treatment with glucocorticoids?

A

Hyperglycemia, HTN, hyperlipidemia, obesity, diabetes, osteopenia, cataracts, growth retardation, poor wound healing, mania and psychosis, increased risk of infection

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72
Q

What can happen if steroid therapy is stopped abruptly?

A

Acute adrenal crisis

73
Q

What are the proliferation inhibitors and anti-metabolites?

A
  1. Azathioprine

2. Mycophenolate mofetil

74
Q

Azathioprine is a pro-drug of ___.

A

6-mercaptopurine

75
Q

What happens after 6-mercaptopurine is formed?

A
  1. Forms 6-TIMP (inhibits de novo purine biosynthesis)
  2. 6-TIMP forms 6-TGTP (inhibits CD28/Rac1 T-cell costimulation)
  3. 6-TGTP is incorporated into DNA, leading to apoptosis

All of these inhibit lymphocyte proliferation

76
Q

When is Azathioprine indicated?

A
  1. Prophylactic prevention of graft rejection following organ transplantation
  2. Autoimmune diseases (RA, Chron’s, MS)
77
Q

What are the AE of Azathioprine?

A

Diarrhea, nausea, vomiting, leukopenia, thrombocytopenia, hepatotoxicity, increased risk of infections/malignancy

78
Q

What drugs interact with Azathioprine and how?

A

Allopurinol and feboxustat - xanthine oxidase inhibitors used in the treatment of gout.

By inhibiting xanthine oxidase, 6-mercaptopurine is elevated, leading to increased toxicity

79
Q

Mycophenolate mofetil (MMF) is a prodrug of ___.

A

Mycophenolic acid (MPA)

80
Q

What is MPA?

A

Non-competitive reversible inhibitor of inosine monophosphae dehydrogenase (IMPDH) type II

81
Q

What is IMPDH type II?

A

Rate-limiting enzyme in the de novo synthesis of purine nucleotides (required for S phase); relevant because this selectively inhibits lymphocyte proliferation

82
Q

When is MMF indicated?

A

On-label: prevent graft rejection following organ transplantation
Off-label: some autoimmune diseases (Phemphigus vulgaris, SLE, MG, psoriasis, Behcet’s disease, lupus nephritis)

83
Q

What is the unique AE of MMF? What are the others?

A

Unique: progressive multifocal leukoencephalopathy caused by reactivation of JC virus

Other: diarrhea, nausea, vomiting, leukopenia, anemia, embryo/fetal toxicity, increased risk of infections/malignancies

84
Q

When is MMF contraindicated and what drug is preferred in these situations?

A

Pregnancy, women of child bearing age, men who wish to become fathers; Azathioprine

85
Q

What are 3 other anti-proliferative drugs used for immunosuppression?

A
  1. Methotrexate
  2. Cyclophosphamide
  3. Chlormabucil

Note: all contraindicated in pregnancy

86
Q

What is the MOA of methotrexate?

A

Inhibition of dihydrofolate reductase indirectly inhibits purine/pyrimidine synthesis

87
Q

Methotrexate is used for autoimmune diseases, especially ___.

88
Q

What is the MOA of cyclophosphamide?

A

Nitrogen mustard alkylating agent crosslinks DNA, RNA, and proteins

89
Q

Cyclophosphamide is used to prevent acute graft rejection and GvHD, and is reserved for ___.

A

The most severe diseases (lupus nephritis, systemic vasculitis, etc.)

90
Q

What is the MOA of chlormabucil?

A

Nitrogen mustard alkylating agent crosslinks DNA, RNA, and proteins

91
Q

What are the two types of immunophilin-binding drugs?

A
  1. Calcineurin inhibitors

2. mTOR inhibitors

92
Q

What are the two calcineurin inhibitors?

A

Cyclosporin and Tacrolimus

93
Q

What are the two mTOR inhibitors?

A

Sirolimus and Everolimus

94
Q

What are the indications of calcineurin inhibitors?

A
  1. Prevent solid organ rejection
  2. Prevent GvHD in BMT
  3. Autoimmune diseases (severe psoriasis, severe RA, SLE, IBD, nephrotic syndrome , eczema, dermatitis, eye conditions)
95
Q

What is the MoA of cyclosporine and tacrolimus?

A
  1. Cyclosporin and tacrolimus readily enter the cell and bind to cyclophilin and FBKP, respectively.
  2. The complexes interact with calcineurin inhibiting its phosphatase activity and preventing the activation fo NFAT and subsequent expression of IL-2.
96
Q

Cyclosporin and tacrolimus inhibit ___ of T-cell activation.

97
Q

Cyclosporin binds to the immunophilin ___; tacrolimus finds to ___.

A

Cyclophilin; FKBP

98
Q

Cyclophilin and FKBP are enzymes known as ___. What do they do? How is this involved in immunosuppression?

A

Peptidylprolyl isomerases (PPIases); catalyze isomerization of peptide bonds containing proline residues; it is unrelated

99
Q

Discuss the PK of calcineurin inhibitors.

A

Extensively metabolized by CYP450 3A4

Poor oral bioavailability

Extensive distrubtion (lipophilic)

100
Q

What are the most significant AE of calcineurin inhibitors?

A

Nephrotoxicity and HTN

Other: neurotoxicity/tremor, glucose intolerance, hyperlipidemia, hirsutism, hypertrichosis, alopecia, hyperK/Mg2+, gum hyperplasia, increased risk of infection/malignancy

101
Q

What drugs increase the potential risk of toxicity of calcineurin inhibitors?

A

Inhibitors of CYP3A4 (grapefruit juice, azole anti-fungals, erytrho/clarithromycin, verapamil, diltiazem)

102
Q

What drugs increase the potential risk of graft rejection when using calcineurin inhibitors?

A

Inducers of CYP3A4 (rifampin, carbamazepine, phenobarbital, phenytoin, St. John’s wort)

103
Q

What is the MOA of mTOR inhibitors?

A

Bind FKBP, form complex which binds and inhibits the mTOR kinase complex downstream of IL-2 receptor. This inhibits IL-2 mediated signals

104
Q

Sirolimus and Everolimus inhibit ___ of T-cell activation.

105
Q

What are the indications of mTOR inhibitors?

A
  1. Prophylactic prevention of graft rejection
  2. Prevention of GvHD
  3. Included in coronary stents to inhibit re-stenosis by preventing cell proliferation
106
Q

mTOR inhibitors are not recommended for liver transplants due to increased risk of ___.

A

Hepatic artery thrombosis

107
Q

mTOR inhibitors are not recommended for lung transplants due to increased risk of ___.

A

Anastomotic dehiscence

108
Q

What are the AE of mTOR inhibitors?

A

Hypertriglyceridemia, hypercholesterolemia, pulmonary edema/lung disease, increased risk new onset diabetes, anemia, thrombocytopenia leukopenia, decreased wound healing, increased risk of infection/malignancy, teratogenic effects

109
Q

What are the drug interactions of mTOR inhibitors?

A

Similar to cyclosporine and tacrolimus

110
Q

What are the immune checkpoint inhibitors for cancer immunotherapy?

A

Ipilimumab

Pembrolizumab/Nivolumab

111
Q

What is Ipilimumab?

A

Monoclonal Ab specific for the CTLA4 protein expressed on activated T cells

112
Q

What is CTLA4?

A

Negative regulatory protein that is upregulated on activated T cells that binds with high affinity to CD80 and CD86, thereby attenuating CD28-dependent co-stimulation and delivering an inhibitory signal to the T cell

113
Q

What is the MOA of Ipilimumab?

A

Binding to CTLA4:

  1. Prevents CTLA4 from binding to CD80/86
  2. Prevents CTLA4 from delivering a negative signal
  3. Leaves CD28 co-stimulation intact

Enhanced T-cell activation

114
Q

What are the indications of Ipilimumab?

A

Late stage melanoma

115
Q

What are the AE of Ipilimumab?

A

Inflammation of skin, GI tract, liver, nerves, and adrenal glands

Treat with high dose steroids

116
Q

What are the indications of pembrolizumab (Keytruda) and nivolumab?

A

Treatment of aggressive metastatic cancer (melanoma, colorectal, head/neck, hepatocellular carcinoma, renal cell caner, large cell lung cancer)

117
Q

What is the MOA of pembrolizumab and nivolumab?

A

Ab specific for the negative regulatory PD1 protein expressed on T-cells

PD1 stimulation normally inhibits T-cell activation

These drugs block PD1/PD-L1 interactions, preventing negative signaling and leading to enhanced T cell immune responses against the cancer cell

118
Q

What are the AE of pembrolizumab and nivolumab?

A

Lung, liver, colon, kidney, skin, pituitary, thyroid, and panreas immune reactions

Treat with high dose steroids

119
Q

What are the drugs used in the treatment of Relapse-Remitting MS?

A
  1. Fingolimod
  2. Natalizumab
  3. Interferon beta
  4. Galtiramer acetate
#1/2 - effective but bad AE
#3/4 - less effective but safer
120
Q

What is the MOA of fingolimod?

A

Activates spingosine-1 phsophate receptor expressed on lympohcytes, sequestering them in the lymph nodes and preventing CNS access

121
Q

What are the AE of fingolimod?

A

Risk of bradyarrhythmia and AV block, risk of varicella zorster virus infection

122
Q

What is the MOA of natalizumab?

A

Anti-alpha4 integrin Ab blocks entry of lympohcytes into the CNS

123
Q

What are the AE of natalizumab?

A

Increased risk of progressive multifocal leukoencephalopathy (PML)

124
Q

What is the MOA of interferon beta?

A

Reduce entry of inflammatory cells into the CNS and reduce T cell activation

125
Q

What is the MOA of glatiramer acetate?

A

Mixture of polymers of 4 amino acids found in myelin basic protein; promotes production of specific suppressor T cells that migrate to the brain and produce bystander suppression at sites of inflammation

126
Q

What is IVIG and what is it used for?

A

Purified human Ig used to prophylactically provide passive immunity to individuals with underlying immunodeficiency diseases

127
Q

What is hyperimmune Ig and what is it used for?

A

Similar to IVIG, but purified from individuals with high titers against a specific Ag or organism

Used for Hep B, CMV, rabies, tetanus, botulism, diphtheria, varciella zoster, snake/scorpion bites

128
Q

What is Rho(D) Ig and what is it used for?

A

Ab specific for the D antigen on RBCs, used to prevent hemolytic disease of the newborn in Rh-negative women

129
Q

Why is multi-drug therapy used to treat active TB?

A
  1. Enhance rates of response/cure

2. Reduce emergence of resistance

130
Q

What are the 4 first line drugs used to treat TB, often used in combination?

A
  1. Isoniazid HCl (INH)
  2. Rifampin
  3. Ethambutol
  4. Pyrazinamide (PZA)
131
Q

INH is a prodrug activated by ___.

A

Catalase peroxidase (TB katG gene)

132
Q

INH targets the ___ gene product, which leads to fatty acid synthesis of cell wall mycolic acid.

A

inhA gene product

133
Q

INH is ___ for replicating organisms and ___ for resting organisms.

A

Bactericidal; bacteriostatic

134
Q

What are two mechanisms of resistance to INH?

A
  1. Mutations in the katG gene that prevent INH activation

2. Mutations in the inhA gene that allow cell wall synthesis to proceed

135
Q

How is INH distributed?

A

Widely, includes CSF, particularly when inflammed

136
Q

What are the AE of INH?

A
  1. Hepatotoxicity (sympomatic hepatitis in some)
  2. Neurotoxicity (peripheral neuritis)
  3. Hypersensitivity reactions (fever, rash, lupus-like, +ANA)
137
Q

What reduces incidence of neurotoxicity in INH treatment?

A

Pyridoxine (vitamin B6) therapy

138
Q

INH + ___ (drug) increases occurrence of hepatitis.

139
Q

INH reduces clearance of ___, leading to toxicity.

140
Q

INH decreases ___ levels and ___ activity.

A

Itraconazole; levodopa

141
Q

What organisms does Rifampin target?

A

GP (Staph, etc.)

142
Q

Rifampin is used as single drug therapy prophylaxis for ___.

A

Meningitis (N. meningitidis)

143
Q

What is the MOA of Rifampin?

A

Inhibits DNA-dependent RNA polymerase, encoded by the rpoB gene

144
Q

What causes Rifampin resistance?

A

rpoB mutations

145
Q

Rifampin is ___ to all populations of organisms.

A

Bactericidal

146
Q

Discuss the distribution of Rifampin.

A

Penetrates most tissues well, good CSF normally and when inflamed

147
Q

What are the AE of Rifampin?

A
  1. Hepatotoxicity
  2. Red discoloration of body fluid (urine, tears, soft contacts)
  3. Acute renal failure, interstitial nephritis
  4. Influenza syndrome (more common with intermittent dosing)
  5. Thrombocytopenia
  6. Cholestatic jaundice
148
Q

Rifampin is a heavy ___ of hepatic microsomal enzymes.

A

Inducer (accelerates clearance of these drugs)

149
Q

What is the MOA of Ethambutol?

A

Inhibits TB arabinosyl transferase encoded by the embB gene, affecting cell wall synthesis; helper drug that inhibits resistance to other drugs

150
Q

Ethambutol is ___ (static vs. cidal)

151
Q

Discuss the distribution of Ethambutol.

A

Good, except CSF levels (even when inflamed)

152
Q

What are the AE of Ethambutol?

A
  1. Optic neuritis (blurred vision, central scotomata, red-green color vision loss)
  2. Peripheral neuropathy
153
Q

What is the MOA of PZA?

A

Prodrug activated by TB pyrazinamidase, enocded by pncA

154
Q

PZA is ___ (cidal vs. static).

155
Q

Discuss the distribution of PZA.

A

Good, including CSF

156
Q

What are the AE of PZA?

A
  1. Hepatitis
  2. Skin rash, GI intolerance
  3. Increased serum uric acid levels (acute gout is uncommon)
157
Q

What is the second line TB drug?

A

Streptomycin

158
Q

What is the MOA of Streptomycin?

A

Inhibits protein synthesis by binding to the ribosome

159
Q

What are the AE of Streptomycin?

A
  1. Ototoxicity

2. Nephrotoxicity

160
Q

What is primary resistance?

A

Resistance acquired at infection (TB itself is drug resistant)

161
Q

What is secondary resistance?

A

Resistance developed during therapy (from ineffective therapy)

162
Q

The risk of evolution of resistance to two drugs is…

A

…the product of the risk of the development of resistance to each drug.

163
Q

What is multi-drug resistant TB?

A

TB that is resistant to both INH and Rifampin

164
Q

What populations have multi-drug resistant TB most commonly?

A

Patients with HIV

165
Q

If the TB is resistant to rifampin, how does the therapy change?

A

Eliminates short-course (6 month), requires therapy for at least 18-24 months

(IPE)

166
Q

What is extensively drug resistant TB?

A

Resistance to INH, Rifampine, FQs, 1 of 3 injectables (amikacin, kanamycin, capreomycin)

167
Q

What is the initial phase and continuation phase of 6-month TB treatment?

A

Initial: RIPE
Continuation: RI

168
Q

How is INH mono-resistant TB treated?

A

REP for 6 bmonths

169
Q

How is PZA monoresistant TB treated?

A

9 months of therapy

170
Q

What is the fundamental strategy of treating TB?

A
  1. Use at least 2 drugs to which the patient’s TB strain is susceptible
  2. Use only drugs that have never been used in the patient before
171
Q

How is LTBI treated?

A
  1. INH monotherapy for 9 months
  2. Rifampin 4 month daily therapy (more expensive but better adherence)
  3. INH + Rifapentene for 3 months, 12-doses, one weekly, DOT regiment
172
Q

How is M. avium (intracellular) treated?

A

Rifampin, Ethambutol + clarithro/azithromycin for 1 year after sputum culture conversion to negative

Resistant to INH and PZA

173
Q

How is M. kansasii treated?

A

RIE for 1 year after sputum culture conversion to negative

Resistant to PZA

174
Q

How is rapidly growing mycobateria treated?

A

Resistant to all first line

1-3 months of cefoxitin/amikacin or imipenem/amikacin

12-18 months of clarithro/azithro + FQ

175
Q

What drugs are active against TB only?

176
Q

Which drugs are active against NTM only?

A

Clarithro

Azithro

177
Q

What drugs are active against TB and NTM?

A

Rifampin
Ethambutol
FQ
AG

178
Q

How is Paucibacillary leprosy treated?

A

Rifampin + Dapsone daily for 12 months

179
Q

How is Multibacillary leprosy treated?

A

Rifampin + Dapsone + Clofazimine daily for 24 months

PT 1 (34 decks)

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