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MOHDIII - Unit 2 > Immunomodulatory & Anti-Inflammatory Drugs > Flashcards

Immunomodulatory & Anti-Inflammatory Drugs Flashcards

1
Q

Target of anti-inflammatory agents

A

Inhibit innate immunity

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2
Q

Target of disease-modifying antifheumatic agents (DMARDs)

A

both innate and adaptive but more often affect inflammatory cytokines (innate)

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3
Q

Receptor protein for IL-2 on activated T cells

A

CD25

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4
Q

Importance of IL-2

A

clonal expansion

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5
Q

TH1 response

A
  • Interferon-gamma (IFN-y)
  • Increases cell mediated cytotoxicity
  • Effective against intracellular pathogens
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6
Q

TH2 response

A
  • IL-4
  • Humoral response, associated w/ production of IgE type antibodies
  • Effective against multicellular parasites
  • Associated w/ allergic diseases
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7
Q

TH17 response

A
  • IL-17
  • Inflammatory responses
  • Effective against extracellular bacteria & fungi
  • Associated w/ autoimmune diseases
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8
Q

Immunostimulants

A

promote activation of the immune system

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9
Q

Adverse effects of immunostimulants

A

systemic inflammatory reactions & flu-like symptoms (fever, chills, etc.)

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10
Q

Applications of immunostimulants

A
  • enhanced vaccination response (adjuvants)
  • chronic infectious disease
  • immunodeficiency disorders
  • cancer
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11
Q

Limitations of immunostimulants

A
  • don’t promote specific immune reactions
  • alternative therapies more effective
  • cytokines require parenteral administration, have short half-lives, expensive
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12
Q

Types of immunostimulants

A

adjuvants & cytokines

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13
Q

Two adjuvants

A

Alum & BCG

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14
Q

Alum adjuvant

A
  • aluminum salts
  • MOST COMMON ADJUVANT IN HUMAN VACCINES
  • support prolonged exposure to developing immune reactions
  • may directly increase activity of APCs
  • few side effects
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15
Q

BCG adjuvant

A
  • live attenuated bacillus calmette-guerin
  • interact directly w/ PRRs and increase APC activity
  • used as an anti TB vaccine & ppl who get this test will test + for TB
  • useful in some cancer therapies (bladder cancer)
  • direct activation of leukocytes can produce a systemic inflammatory response and septic shock
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16
Q

Cytokine immunostimulants

A

IL-2 (aldesleukin), interferons

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17
Q

IL-2 (aldesleukin) cytokine immunostimulant

A
  • increased proliferation of activated T cells, production of IFN-y, & cytotoxic killer cell activity
  • treatment of metastatic melanoma & renal cell carcinoma
  • associated w/ serious capillary leak syndrome, hypotension, reduced organ perfusion…CAN BE FATAL
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18
Q

Interferon cytokine immunostimulants

A
  • INF-y: stimulates cell mediated cytotoxic immune response; treat sever infections
  • IFN-alpha & beta: produced by most cells in response to viral infection; useful in treating chronic viral infection (hepatitis)
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19
Q

Clinical indications for suppression of immune responses

A
  • organ transplantation
  • treatment of inflammatory disorders
  • treatment of autoimmune disorders
  • selective immunosupression
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20
Q

Adverse effects common to ALL general immunosuppressants

A
  • increased infection risk
  • increased risk of cancer: loss of immune surveillance & increased susceptibility to tumor-promoting pathogens
  • other adverse effects are mechanism specific
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21
Q

Cyclophosphamide

A
  • immunosuppression via cross linking DNA & killing proliferating cells thus preventing expansion of antigen specific lymphocytes
  • uses: auto-immune diseases, bone marrow transplant
  • adverse effects: myelosupression, nausea, vomiting, infertility
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22
Q

Azathiopurine

A
  • metabolized to 6-mercaptopurine & 6-thioguanine
  • inhibit purine synthesis & cause DNA damage when incorporated into DNA as thio-guanine nucleotide
  • inactivated by xanthine oxidase (decreased when combined with allopurinol-requires reduced dosage)
  • uses:renal & other tissue transplantation, auto-immune disorders (lupus, rheumatoid arthritis)
  • adverse effects: myelosuppression, nausea, vomiting
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23
Q

Mycophenolate Mofetil

A
  • hydrolyzed to mycophenolic acid
  • inhibits inosine monophosphate dehydrogenase preventing purine synthesis
  • uses: solid organ transplant as an alternative to cyclosporine, auto-immune diseases
  • adverse effects: myelosuppression, nausea, vomiting
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24
Q

Methotrexate

A
  • inhibits dihydrofolate reductase
  • direct inhibition & accumulated inhibitory intermediates prevent synthesis of thymidine as well as purine nucleotides
  • uses: RHEUMATOID ARTHRITIS, auto-immune diseases
  • adverse effects: nausea, mucosal ulcers, modest hepatotoxicity, myelosuppression
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25
Q

Leflunomide

A
  • metabolized to A77-1726
  • inhibits dihydroorotate dehydrogenase leading to decrease PYRIMADINE synthesis
  • suject to enterohepatic recirculation & has half-life of 19 days
  • uses: similar to methotrexate
  • adverse effects: diarrhea, modest hepatotoxicity, myelosuppression
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26
Q

Glucocorticosteroid effects (Prednisone)

A
  • anti-inflammatory

- immunosuppressive

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27
Q

Prednisone mechanisms

A
  • induced transcription: annexins (lipocortins) –inhibition of PLA2, & synthesis of lipid derived mediators
  • repressed transcription: IL-1,2,3,5, TNF, IFNy, GM-CSF – reduced T helper cell mediated response, B cell antibody production, cytotoxic response
  • repressed transcription: cyclooxygenase, NO synthase, PLA2 – reduced mediator release
  • repressed transcription: IL-8, other chemotaxins – reduced recruitment of leukocytes
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28
Q

Prednisone usage

A
  • solid organ & hematopoetic stem cell tranplant

- combined anti-inflammatory/immunosuppressant activity (asthma, allergic reactions, systemic inflammation)

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29
Q

Prednisone adverse effects

A
  • only with greater than 2 weeks daily systemic administration
  • cushings syndrome, glucose intolerance, ocular disturbance, GI disturbances, NO SERIOUS MARROW TOXICITY, osteoporosis, hypertension, psychiatric disturbances
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30
Q

Target of immunomodulatory agents

A

T & B cells

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31
Q

Role of calcineurin in T cell signaling

A

de phosphorylates NF-AT so then it can activate transcription in the nucleus

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32
Q

Calcineurin inhibitors

A

cylcosporine - binds w/ cyclophilin and inhibits

tacrolimus (FK506) - binds w/ FKBP12 & inhibits

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33
Q

Cyclosporine

A
  • often combined w/ other immuno-suppressants
  • useful in kidney, liver, & cardiac transplants
  • useful in rheumatoid arthritis, & inflammatory diseases (ABD, asthma)
  • adverse effects: nephrotoxicity, increased cancer incidence documented
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34
Q

Tacrolimus (FK506)

A
  • same uses and toxicities as cyclosporine

- 10-100 TIMES MORE POTENT than cyclosporine

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35
Q

IL-2 receptor signaling pathway

A
  • uses mTOR

- takes 45 min

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36
Q

Sirolimus (rapamycin)

A
  • usually combined w/ other agents
  • inhibits mTOR in IL-2 signaling pathway
  • useful in steroid resistant graft versus host disease in hematopoetic stem cell transplants
  • antagonizes tacrolimus but synergizes w/ cyclosporine
  • adverse effects: myelosuppression (not combined with anti metabolite due to syngergy), hyperlipidemia, HTN, edema, hepatotoxicity
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37
Q

Use of therapeutic antibodies

A
  • provides “passive immunity” before host adaptive immune responses can be effective (hepatitis, rabies, tetanus), or when host immunization is unwanted (Rho[D]) – acts like host adaptive immunity
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38
Q

Administration of therapeutic antibodies

A
  • All applications require parenteral administration, but long half-lives can allow weekly - monthly dosing for continuous effect
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39
Q

Human derived antibody (Rh(D) immune globulin, adalimumab)

A
  • activate human complement leukocytes: YES
  • induce anti-antibody response: NO
  • adverse effects: few
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40
Q

Animal derived antibody (ATG, OKT3)

A
  • activate human complement leukocytes: YES
  • induce anti-antibody response: YES
  • adverse effects: on repeated use antibody destruction allergic reaction serum sickness
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41
Q

Chimeric “humanized” derived antibody (basiliximab, alemtuzumab, infliximab)

A
  • activate human complement leukocytes: YES
  • induce anti-antibody response: NO
  • adverse effects: few
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42
Q

Fc-fusion protein derived antibody (belatacept, etanercept)

A
  • activate human complement leukocytes: variable, usually not complement, Fc confers extended half life (weeks)
  • induce anti-antibody response: NO
  • adverse effects: few
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43
Q

Treatment of Rh hemolytic disease

A
  • Rh(D) immune globulin (BayRho-D, WinRho SDF)
  • maternal administration of immune globulin prevents initiation of maternal immune response to fetal Rh(D) antigen
  • works through opsonization, also inhibit naive Rh(D) reactive B cells, & T cell responses are NOT affected but are not harmful to fetus
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44
Q

Blocking receptors preventing T cell activation

A
  • anti-T cell globulin (ATG): targets T cells for destruction
  • Belatacept: immunosuppressant approved for kidney transplantation
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45
Q

Belatacept

A
  • fusion protein of B7 ligand (CTLA4) w/ an IgG Fc domain
  • second generation version of abatacept w/ higher affinity for B7
  • FDA approved for kidney transplantation 2011
  • prevents interaction b/w B7 on APC and CD28 on T cell
  • adverse effects: anemia, neutropeina, peripheral edema, posttransplant lymphoproliferative disorder (PTLD)
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46
Q

Anti-T cell globulin (ATG)

A
  • blocks T cell surface receptors & opsonizes T cells
  • adverse effects: cytokine release syndrome, CAN BE REDUCED BY PRE-TREATMENT WITH ACETAMINOPHEN & ANTIHISTAMINE
  • produces prolonged T cell depletion (more than a year), potential for late rejection as lymphoid system recovers
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47
Q

Anti-CD52

A
  • surface protein expressed on T & B cells, monocytes, macrophages, and NK cells
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48
Q

Alemtuzumab

A
  • humanized anti-CD52 antibody
  • depletes broad variety of cells involved in immune reactions
  • adverse effects: myelosuppression, flu-like symptoms
  • effect: produces prolonged depletion of T cell and other cells of immune system (one year)
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49
Q

Basiliximab

A
  • anti CD25 (IL-2 receptor)
  • blocks and opsonizes alpha chain of CD25 on ACTIVATED T cells
  • adverse effects: well tolerated
  • effect: depletes only activated T cells, moderate compared to ATG (more appropriate for patients w/ low to moderate risk of rejection)
  • reduced immune depletion is associated w/ reduced incidence of infection (particularly chronic CMV infection) & malignancy
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50
Q

Anti-TNF alpha agents

A
  • infliximab
  • adalimumab
  • etanercept
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51
Q

Infliximab

A
  • humanized antibody to TNF alpha
  • applications: inflammatory disease involving TNFalpha, PARENTERAL ADMINISTRATION REQUIRED, rheumatoid arthritis w/ methotrexate, & crohn’s disease w/ azathioprine
  • complications: increased frequency of infections
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52
Q

Adalimumab

A
  • human antibody to TNF alpha

- similar to infliximab

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53
Q

Etanercept

A
  • fusion protein containing ligand binding domain of TNFalpha receptor & the Fc domain of human IgG
  • similar to infliximab
54
Q

Anti IL-1 agents

A
  • anakinra
55
Q

Anakinra

A
  • competitive IL-1 receptor antagonist
  • uses: rheumatoid arthritis
  • short half life, daily injection required
  • complications: increased infection susceptibility
56
Q

Protein required by cytokine receptors

A

Jak

57
Q

Jak inhibitor

A

tofacitinib

58
Q

Tofacitinib

A
  • jak kinase inhibitor
  • uses: rheumatoid arthritis 2012, second line for those failing methotrexate
  • administration: oral
  • mechanism: inhibits activity of cytokines required for adaptive immunity (IL-2, IL-4, IL-6)
  • adverse effects: anemia, neutropenia, myelosuppressino, increased risk of infection (HERPES ZOSTER)
59
Q

Mediators released from activated leukocytes

A
  • prostaglandins, leukotrienes

- histamine

60
Q

Prednisone

A
  • increase annexin production
  • annexin inhibits PLA2 inhibiting production of prostaglandins/leukotrienes
  • decreased recruitment of leukocytes
61
Q

NSAIDS

A
  • inhibit cyclooxygenase

- lowers prostaglandin levels decreasing inflammation

62
Q

Zileuton

A
  • inhibits lipoxygenase

- lowers leukotriene levels decreasing inflammation

63
Q

Comolyn & Nedocromil

A
  • inhibit histamine release

- decreases inflammation

64
Q

Degradation of histamin requires two enymes

A
  • imidazol N methyltransferase

- diamine oxidase

65
Q

Importance of diamine oxidase

A
  • histamine intolerance results from deficiency or reduced activity of diamine oxidase
  • anything that effects activity of diamine oxidase will effect half life of histamine
66
Q

Sites of histamine production and storage

A
  • synthesized in most tissues
  • stored: complexed with sulfated polysacchrides, mast cells/basophils (heparin), fibroblasts (chondroitin sulfate)
  • IgE antibody reactions promote histamine release from mast cells in type I hypersensitivity reactions (allergy, anaphylaxis)
67
Q

Histamine & CNS

A
  • neurotransmitter
  • neurons in posterior hypothalamus
  • projections to: neuroendocrine releasing neurons, cardiovascular areas, thermoregulatory regions, “AROUSAL” REGIONS (promotes wakefulness)
68
Q

Histamine receptors

A
  • H1: smooth muscles, enothelium, cardiac muscle, sensory nerve terminals, CNS post synaptic; Gq coupled
  • H2: gastric parietal cells, mast cells, cardiac muscle, CNS post synaptic; Gs coupled-INCREASED cAMP
  • H3: CNS pre synaptic; Gi coupled-DECREASED cAMP
  • H4: CD4 T cells, eosinophils, neutrophils; Gi coupled-DECREASED cAMP
69
Q

Vascular smooth muscle histamine response

A
  • H1/H2 receptor
  • NO release promotes smooth muscle relaxation & vasodilation
  • symptom: hypotension, flushing, headache, anaphylaxis
70
Q

Endothelium histamine response

A
  • H1 receptor
  • induced actin/myosin contraction, separation of endothelial cells
  • symptom: edema
71
Q

Cardiac muscle histamine response

A
  • H1/H2 receptor
  • H1: decreased rate and atrial contractility
  • H2: increased rate and contractility
  • symptom: unclear
72
Q

Bronchiolar smooth muscles histamine reaction

A
  • H1 receptor
  • constriction
  • symptom: decreased airway size leading to breathing difficulty
73
Q

Uterine smooth muscle histamine resoponse

A
  • H1 receptor
  • constriction
  • symptom: premature labor w/ anaphylaxis
74
Q

Gastric smooth muscle histamine response

A
  • H1 receptor
  • constriction
  • symptom: diarrhea
75
Q

Sensory nerves histamine response

A
  • H1 receptor
  • stimulation
  • symptom: pain, itching
76
Q

CNS hypothalamus histamine response

A
  • H1 receptor
  • arousal
  • symptom: increased wakefulness
77
Q

CNS emetic center histamine response

A
  • H1 receptor
  • emesis
  • symptom: nausea, vomiting
78
Q

CNS histamine response

A
  • H1/H2 receptor

- effects on thirst, blood pressure, perception of pain

79
Q

Gastric secretion histamine response

A
  • H2 receptor
  • increased acid production, pepsin, intrinsic factor
  • symptom: mucosal erosion, ulceration
80
Q

Histamine “triple response”

A
  • “wheal and flare” response
  • wheal = edema
  • reddening from dilation of small vessels
  • flare = axon reflex; histamine stimulation of sensory nerve terminals cause release of vasodilators at other branches
  • ithcing
81
Q

Ways to antagonize histamine effects

A
  • physiologic: epinephrine
  • release inhibitors: cromolyn & nedocromil inhibit Ca2+ dependent release (asthma)
  • receptor antagonist: competitive antagonist of H1 or H2 receptors
82
Q

Comolyn & Nedocromil

A
  • poorly soluble salts: must be topically absorbed (inhaled)
  • only effective prophylactially as part of long term therapy for asthma
  • mechanism: inhibits degranulation of mast cells through inhibition of Ca channels, inhibition of Cl- may also contribute to reduced nerve activity & inhibition of cough
83
Q

H1 receptor antagonists

A
  • act as inverse agonists; reduce basal levels of activity
  • uses: allergic rhinitis & utricaria, motion sickness/emesis
  • adverse effects: sedation w/ first generation, Non H1 effects:dry mouth, urinary retention, tachycardia (anticholinergic), orthostatic hypotension (adrenoreceptor), increased appetite (serotonin block), blocks sodium channels (local anesthesia)
84
Q

First generation antihistamines

A
  • diphenhydramine: motion sickness
  • dimenhydrinate: motion sickness
  • cyclizine: motion sickness
  • promethazine: antiemetic
85
Q

Second generation antihistamines

A
  • poor penetration into CNS reducing sedative effects

- loratadine, cetrizine, fexofenadine

86
Q

Role of phospholipase A2 (PLA2)

A
  • enzyme that turns membrane phospholipids (phosphatidylcholine) into aracadonic acid
87
Q

Role of cyclooxygenase

A
  • enzyme that turns AA into prostaglandins
88
Q

Role of lipoxygenase

A
  • enzyme that turns AA into leukotrienes
89
Q

Prostanoid synthesis & degradation

A
  • short half lives and lack to stored products make prostanoid activity synthesis dependent
  • membrane permeable and passively released after synthesis
  • autocrine and paracrine activity
90
Q

Prostanoids

A
  • prostacyclin (PGI2)
  • prostaglandin (PGE2)
  • thromboxane (TXA2)
91
Q

PGE2

A
  • prostaglandin
  • synthesis: most tissues
  • half life: 30 sec
92
Q

PGI2

A
  • prostacyclin
  • synthesis: endothelium, vascular smooth muscle
  • half life: 3 min
93
Q

TXA2

A
  • thromboxane
  • synthesis: platelets, macrophages
  • half life: 30 sec
94
Q

PGE2 Gs receptor effects

A
  • blood vessels: dilate
  • smooth muscle: relax
  • platelets: none
  • pain: hyperalgesia
  • hypothalamus: increased body temp
95
Q

PGE2 Gq receptor effects

A
  • blood vessels: none
  • smooth muscle: constrict (uterine)
  • platelets: none
  • pain: none
  • hypothalamus: increased body temp
96
Q

PGI2 Gs receptor effects

A
  • blood vessels: dilate
  • smooth muscle: relax (bronchial/uterine)
  • platelets: inhibits aggregation
  • pain: hyperalgesia
  • hypothalamus: none
97
Q

TXA2 Gq receptor effects

A
  • blood vessels: constrict
  • smooth muscle: constrict (bronchial)
  • platelets: stimulates aggregation
  • pain: none
  • hypothalamus: none
98
Q

Cyclooxygenase-1 (COX-1)

A
  • substrates: narrow specturm-arachidonate

- indelibility: not inducible, constitutively expressed

99
Q

Cyclooxygenase-2 (COX-2)

A
  • substrates: broader spectrum-arachidonate, linolenic, unsaturated C22 FAs
  • indelibility: highly inducible, inducers: IL-1, TNFalpha, LPS; inhibitors: IL-4, IL-10, IL-13
100
Q

Compare COX-1 & COX-2

A
  • steady state for most cells, COX-1»»»»»»»»>COX-2
  • COX-2 has larger role in kidney & uterus
  • elevated prostanoid production associated w/ inflammation due to COX-2
101
Q

Non-selective NSAID therapeutic applications

A
  • fever
  • analgesia
  • inflammation due to injury or stress
  • rheumatoid & osteoarthritis
  • cardiovascular prophylaxis, reduced platelet aggregation (aspirin only)
102
Q

Aspirin (Acetylsalicylic Acid, ASA)

A
  • metabolism: rapidly converts to salicylic - acetyl group is active part of ASA and is what separates it from other NSAIDs
  • more COX-1 inhibition, so if you give enough to get COX-2 will always get COX-1 inhibitions too
  • biochemical effects: ASA acetylates & IRREVERSIBLY inhibits, while salicylic acid REVERSIBLY inhibits
103
Q

Keotolac

A
  • NSAID
  • 395 selectivity
  • post surgical analgesic
104
Q

Indomethacin

A
  • NSAID
  • 10 selectivity
  • arthritis, anti imflammatory
105
Q

Aspirin

A
  • NSAID
  • 4.4 selectivity
  • cardiovascular prophylaxis
106
Q

Naproxen

A
  • NSAID
  • 3.8 selectivity
  • anti inflammatory
107
Q

Ibuprofen

A
  • NSAID

- 2.6 selectivity

108
Q

Diclofenac

A
  • NSAID
  • .3 selectivity
  • arthritis/anti inflammatory
109
Q

Etodolac

A
  • NSAID
  • .1 selectivity
  • arthritis
110
Q

Meloxicam

A
  • NSAID
  • .04 selectivity
  • arthritis
111
Q

NSAID anti inflammatory effects

A
  • block production of prostanoids by inhibition of COX

- COX-2 primarily responsible for prostanoid production during inflammation

112
Q

NSAID analgesic effects

A
  • reduced PGE2 & PGI2 induced hyperalgesia
  • general reduced inflammation
  • not effective against non inflammatory pain (distention of hollow organs)
  • not as efficacious as other analgesic
113
Q

NSAID antipyretic effects

A
  • inhibits PGE2 production in CNS stimulated by cytokines (IL-1, IL-6, & TNFalpha)
  • reduced peripheral prostanoids may also reduce cytokine expression from macrophages
  • does NOT influence body temp when elevated by non inflammatory factors (exercise, environmental change)
114
Q

NSAID anti platelet effects

A
  • inhibit platelet COX-1
  • increase bleeding time (increase surgical bleeding)
  • potentiates GI bleeding
115
Q

NSAID (aspirin) cardiovascular protection

A
  • irreversibly inhibits platelet COX-1 (no TXA2 made for life of platelet)
  • platelet COX-1 activity only restored through replacement of platelets over 5-7days
  • other NSAIDs inhibit platelet COX-1, but effect is REVERSIBLE
  • antagonize irreversible anti-platelet activity of ASA, for cardiovascular protection should be taken 30 min before or after other NSAID elimination
116
Q

NSAID GI effects

A
  • inhibition of COX-1 causes lysis of epithelium (misoprostol, PGE1 analog, protects against COX-1 inhibition)
  • GI infection of inflammation induces COX-2
117
Q

NSAID GI toxicity

A
  • dyspepsia: upper abdominal pain, bloating nausea (35%)
  • ulcers: gastric more common than duodenal (16%)
  • GI bleeding: anemia
  • prevention: H2 receptor antagonists (cimetidine, ranitidine, famotidine, nizatidine), PPIs (omeprazole, lansoprazole), misoprostol blocks NSAID induced ulcers but not other anti inflammatory effects
118
Q

NSAID kidney effects

A
  • renal vasoconstriction, water/salt retention (edema, HTN)
  • acute renal failure (.5-1%)
  • at risk patients: CHF, cirrhosis/ascites, age
119
Q

NSAID uterus effects

A
  • both COX-1/2 present
  • PGE2 contracts, PGI2 relaxes
  • NSAIDs can delay premature labor
  • NSAIDs can reduce dysmenorrhea (menstrual cramps)
120
Q

Aspirin intolerance

A
  • salicylism: hypersensitivity to ASA; hyperventilation, tinnitus, vertigo, emesis, sweating
  • reye’s syndrome: ASA used in children w/ viral illness; acute encephalopathy, fatty liver degeneration
121
Q

Acetaminophen

A
  • Non selective COX inhibitor
  • usage: analgesic/antipyretic ONLY, no anti inflammatory activity
  • tolerance: HEPATOTOXICITY with overdose
122
Q

COX-2 selective NSAIDS

A
  • retain COX-2 specific effects: anti inflammatory, antipyretic, analgesic, renal toxicity
  • lack COX-1 effects: platelet, cardio protective, GI side effects
  • usage: osteoarthritis, rheumatoid arthritis
  • expensive
123
Q

NSAID COX-2 selectivity comparison

A

meloxicam

124
Q

Vioxx (rofecoxib) debacle

A
  • reduced incidence of GI effects (only in patients not taking aspirin)
  • adverse effects: increased incidence of cardiovascular events
  • result: Celecoxib (available), rofecoxib (withdrawn), valdecoxib (withdrawn), parecoxib:injectible pro drug of valdecoxib available in europe
125
Q

NSAID cardiovascular risk

A
  • ALL NSAIDS (accept ASA) APPEAR TO BE ASSOCIATED W/ SOME LEVEL OF INCREASED RISK
  • naproxen may be safer
  • mechanism: loss of COX-2 antagonism of platelet activity
126
Q

Leukotrienes

A

LTB4, LTC4, LTD4

127
Q

LTB4 effects

A
  • blood vessels: none
  • smooth muscle: none
  • leukocytes: neutrophil chemotaxis
128
Q

LTC4 effects

A
  • blood vessels: decreased coronary blood flow, increased permeability
  • smooth muscle: bronchial constriction
  • leukocytes: eosinophil chemotaxis & degranulation
129
Q

LTD4 effects

A
  • blood vessels: decreased coronary blood flow, increased permeability
  • smooth muscle: bronchial constriction
  • leukocytes: eosinophil chemotaxis & degranulation
  • primary mediator of bronchial smooth muscle constriction and edema in asthmatic airways
130
Q

Zileuton

A
  • leukotriene (LTB4, LTD4) synthesis inhibitor
  • oral asthma therapy
  • adverse effects: liver toxicity (lower metabolism of other drugs)
131
Q

Zafirlukast & Montelukast

A
  • leukotriene receptor antagonist

- oral asthma therapy

132
Q

Aspirin induced asthma

A
  • 5-10% of asthmatics exhibit sensitivity to aspirin & other NSAIDs
  • NOT A DRUG ALLERGY
  • sensitivity caused by shifting of AA metabolism from prostaglandin to leukotriene synthesis

MOHDIII - Unit 2 (23 decks)

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