Term
| Which enzyme catalyzes the removal of arachidonic acid from membrane phospholipids? |
|
Definition
|
|
Term
| Which enzyme catalyzes the first step of the conversion of arachidonic acid to LTs, HPETEs, and HETEs? |
|
Definition
|
|
Term
| Which enzyme catalyzes the first step in the conversion of arachidonic acid to PGs and TxA2? |
|
Definition
|
|
Term
arachidonic acid -> 5-HPETE Which enzyme catalyzes this reaction? |
|
Definition
|
|
Term
LTA4 --> LTB4 Which enzyme catalyzes this reaction? |
|
Definition
|
|
Term
LTA4 --> LTC4
Which enzyme catalyzes this reaction? |
|
Definition
|
|
Term
| What does LTC4 synthase require to convert LTA4 to LTC4? |
|
Definition
|
|
Term
LTC4 --> LTD4 Which enzyme catalyzes this reaction? |
|
Definition
| γ-glutamyl transpeptidase |
|
|
Term
LTD4 --> LTE4 Which enzyme catalyzes this reaction? |
|
Definition
|
|
Term
|
Definition
|
|
Term
| Which receptors does LTB4 bind to achieve its primary actions? |
|
Definition
|
|
Term
| What receptors do the cysteinyl leukotrienes bind to achieve their primary actions? |
|
Definition
|
|
Term
| What is the primary action of 5-HETE? |
|
Definition
|
|
Term
| What are the primary actions of LTB4? |
|
Definition
| leukocyte chemotaxis, aggregation, adhesion |
|
|
Term
| What are the primary actions of the cysteinyl LTs? |
|
Definition
| vasoconstriction, bronchospasm, increased vascular permeability |
|
|
Term
arachidonic acid --> PGG2 Which enzyme catalyzes this reaction? |
|
Definition
| cyclooxygenase (COX 1 & 2) |
|
|
Term
PGG2 --> PGH2 Which enzyme catalyzes this reaction? |
|
Definition
|
|
Term
| What is the name of the enzyme that has both cyclooxygenase and peroxidase activities? |
|
Definition
|
|
Term
| Which cyclooxygenase is constitutively expressed and performs housekeeping functions? |
|
Definition
|
|
Term
| Which COX enzyme is inducible and is associated with inflammatory responses, fever, and pain? |
|
Definition
|
|
Term
| What are the main actions of PGI2 (prostacyclin)? |
|
Definition
| vasodilation, decreased platelet aggregation |
|
|
Term
| What are the main actions of TxA2? |
|
Definition
| vasoconstriction, increased platelet aggregation |
|
|
Term
| What are the main actions of PGD2, PGE2, and PGF2a? |
|
Definition
| vasodilation, potentiation of edema formation, pain, fever |
|
|
Term
| Which COX enzyme is found in platelets? |
|
Definition
|
|
Term
| Where is COX-2 constitutively expressed? |
|
Definition
| brain, kidney, vas deferens, GI tract |
|
|
Term
| What are the main functions of COX-1? |
|
Definition
housekeeping (cytoprotective, maintains GI mucosa integrity, mediates normal platelet function) |
|
|
Term
| What are the main functions of COX-2? |
|
Definition
| inflammation, memory, water/salt balance, uterine contractions, colon and breast cancer |
|
|
Term
| What induces the expression/action of COX-2? |
|
Definition
| bacterial products (LPS), tissue destruction (O2 radicals), growth factors, inflammatory cytokines |
|
|
Term
| What is COX-2 downregulated by? |
|
Definition
| anti-inflammatory cytokines |
|
|
Term
| Which COX enzyme produces larger amounts of PGs and TxA2? |
|
Definition
|
|
Term
PGH2 --> PGI2 (prostacyclin) Which enzyme catalyzes this reaction? |
|
Definition
|
|
Term
| Where is PGI2 (prostacyclin) normally found? |
|
Definition
|
|
Term
PGH2 --> TxA2 Which enzyme catalyzes this reaction? |
|
Definition
|
|
Term
| Where is TxA2 normally found? |
|
Definition
|
|
Term
PGH2 --> PGD2 Which enzyme catalyzes this reaction? |
|
Definition
|
|
Term
PGH2 --> PGE2 Which enzyme catalyzes this reaction? |
|
Definition
|
|
Term
PGH2 --> PGF2a Which enzyme catalyzes this reaction? |
|
Definition
|
|
Term
| What are the receptors for PGI2 (prostacyclin)? |
|
Definition
|
|
Term
What are the receptors for TxA2? |
|
Definition
|
|
Term
| What are the receptors for PGD2? |
|
Definition
|
|
Term
| What are the receptors for PGE2? |
|
Definition
|
|
Term
| What are the receptors for PGF2a? |
|
Definition
|
|
Term
| What is the general action of PGE2 and PGI2 on smooth muscle? |
|
Definition
|
|
Term
| What is the general action of TxA2 on smooth muscle? |
|
Definition
|
|
Term
| Which eicosanoids mediate "cytoprotective" actions on the GI tract? |
|
Definition
|
|
Term
| Which is the most important eicosanoid with regards to fever and pain? |
|
Definition
|
|
Term
| Which eicosanoid promotes platelet aggregation? |
|
Definition
|
|
Term
| Which eicosanoid inhibits platelet aggregation? |
|
Definition
|
|
Term
| What are the characteristics of acute inflammation? |
|
Definition
| edema, localization of leukocytes (neutrophils) |
|
|
Term
| What are the characteristics of chronic inflammation? |
|
Definition
| involvement of lymphocytes and macrophages, proliferation of blood vessels (angiogenesis) and connective tissue |
|
|
Term
| What are the three major components of acute inflammation? |
|
Definition
1. Change in vascular caliber (vasodilation) 2. Change in microvasculature (more permeable) 3. Emigration of leukocytes out of blood vessels (diapedesis) |
|
|
Term
| What are the four main steps of the emigration of leukocytes out of blood vessels? |
|
Definition
- margination - adhesion - transmigration - chemotaxis |
|
|
Term
| What are the pro-inflammatory interleukins? |
|
Definition
|
|
Term
| What is an anti-inflammatory interkeukin? |
|
Definition
|
|
Term
| What are the pro-inflammatory cytokines and chemokines? |
|
Definition
|
|
Term
|
Definition
Monocyte chemoattractant protein-1 (pro-inflammatory chemokine) |
|
|
Term
|
Definition
| Macrophage inflammatory protein-1α |
|
|
Term
| What are the vasoactive amines involved in inflammation? |
|
Definition
histamine 5-HT (serotonin) |
|
|
Term
|
Definition
| non-steroidal anti-inflammatory drugs |
|
|
Term
| What are the four main groups of NSAIDs? |
|
Definition
| salicylates, propionic acid derivatives, acetic acid derivatives, selective inhibitors of COX-2 |
|
|
Term
| How do NSAIDs alter gene expression? |
|
Definition
| Inhibition of transcription factor NFκB |
|
|
Term
| What is the enzymatic action of the NSAIDs? |
|
Definition
|
|
Term
| Therapeutic uses of NSAIDs |
|
Definition
analgesic, antipyretic, anti-inflammation close ductus arteriosus, prophylactic treatment of thromboembolic disorders |
|
|
Term
| What is the most commonly reported adverse side effect of NSAID administration? |
|
Definition
| gastric or intestinal irritation |
|
|
Term
|
Definition
PGE1 analog used to diminish GI irritation with adminstration of NSAIDs |
|
|
Term
|
Definition
proton pump inhibitor used to decrease GI side effects with NSAID administration |
|
|
Term
| Why do NSAIDs cause increased bleeding time? |
|
Definition
| inhibition of TxA2 in platelets |
|
|
Term
| Why do NSAIDs cause prolonged gestation? |
|
Definition
| decreased PGs affecting uterine contractions |
|
|
Term
| Why do NSAIDS cause renal injury/failure? |
|
Definition
| decreased renal blood flow due to vasoconstriction |
|
|
Term
|
Definition
Acetyl salicylic acid (ASA, aspirin) Sodium salicylate Salicylic acid Methyl salicylate Diflusinsal |
|
|
Term
| Which NSAID is said to be the gold standard of this group? |
|
Definition
| Acetyl salicylic acid (ASA, aspirin) |
|
|
Term
Salicylates (action, uses) |
|
Definition
non-selective inhibition of COX antipyresis, relief of low intensity pain, anti-inflammatory, anti-thrombotic |
|
|
Term
| How is the action of ASA different from the other salicylates? |
|
Definition
| irreversibly inhibits COX-1 & -2 by covalently binding |
|
|
Term
Salicylates (potential adverse side effects) |
|
Definition
CNS stimulation followed by depression Tinnitus, hearing loss Reye's syndrome and lethal drug poisoning (children) Asthma Salicylate poisoning (salicylism) |
|
|
Term
Proprionic acid derivatives (examples) |
|
Definition
Ibuprofen Naproxen Flurbiprofen Ketoprofen |
|
|
Term
Proprionic acid derivatives (action, uses) |
|
Definition
reversible non-selective inhibition of COX antipyresis, analgesia, anti-inflammatory |
|
|
Term
Proprionic acid derivatives (adverse side effects) |
|
Definition
GI effects Rash Tinnitus Peripheral edema (not recommended for pregnant or breastfeeding women) |
|
|
Term
Acetic acid derivatives (examples) |
|
Definition
Indomethacin Sulindac Etodolac Ketorolac Diclofenac Tolmetin |
|
|
Term
Acetic acid derivatives (actions, uses) |
|
Definition
reversible inhibition of COX inhibition of neutrophil migration anti-inflammatory etodolac, ketorolac: perioperative pain |
|
|
Term
Acetic acid derivatives (adverse side effects) |
|
Definition
GI effects severe headache indomethacin: high incidence of severe CNS effects (headache) |
|
|
Term
Selective COX-2 Inhibitors (examples) |
|
Definition
Celecoxib Rofecoxib Valdecoxib Parecoxib Etoricoxib |
|
|
Term
Acetyl salicylic acid (ASA, aspirin) |
|
Definition
NSAID, salicylate irreversible non-selective COX inhibitor |
|
|
Term
|
Definition
NSAID, salicylate reversible non-selective COX inhibitor |
|
|
Term
|
Definition
NSAID, salicylate reversible non-selective COX inhibitor |
|
|
Term
|
Definition
NSAID, salicylate reversible non-selective COX inhibitor |
|
|
Term
|
Definition
NSAID, salicylate reversible non-selective COX inhibitor |
|
|
Term
|
Definition
NSAID, propionic acid derivative reversible non-selective COX inhibitor |
|
|
Term
|
Definition
NSAID, propionic acid derivative reversible non-selective COX inhibitor |
|
|
Term
|
Definition
NSAID, propionic acid derivative reversible non-selective COX inhibitor |
|
|
Term
|
Definition
NSAID, propionic acid derivative reversible non-selective COX inhibitor |
|
|
Term
|
Definition
NSAID, acetic acid derivative reversible non-selective COX inhibitor inhibitor of neutrophil migration |
|
|
Term
|
Definition
NSAID, acetic acid derivative reversible non-selective COX inhibitor inhibitor of neutrophil migration |
|
|
Term
|
Definition
NSAID, acetic acid derivative reversible non-selective COX inhibitor inhibitor of neutrophil migration |
|
|
Term
|
Definition
NSAID, acetic acid derivative reversible non-selective COX inhibitor inhibitor of neutrophil migration |
|
|
Term
|
Definition
NSAID, acetic acid derivative reversible non-selective COX inhibitor inhibitor of neutrophil migration |
|
|
Term
|
Definition
NSAID selective COX-2 inhibitor |
|
|
Term
|
Definition
NSAID selective COX-2 inhibitor |
|
|
Term
|
Definition
NSAID selective COX-2 inhibitor |
|
|
Term
|
Definition
NSAID selective COX-2 inhibitor |
|
|
Term
|
Definition
NSAID selective COX-2 inhibitor |
|
|
Term
|
Definition
para-aminophenol derivative inhibitor of COX activity (weakened by peroxides) analgesic, antipyretic side effects: skin rash, allergic reactions, hepatic necrosis, renal injury/failure |
|
|
Term
|
Definition
Receptor Antagonists: Zafirlukast (ACCOLATE), Montelukast (SINGULAIR) Synthesis inhibitors: Zileuton used in treatment of asthma |
|
|
Term
|
Definition
Leukotriene receptor antagonist asthma treatment |
|
|
Term
|
Definition
Leukotriene receptor antagonist asthma treatment |
|
|
Term
|
Definition
Leukotriene synthesis inhibitor asthma treatment |
|
|
Term
|
Definition
Glucocorticoids Mineralocorticoids Adrenal androgens |
|
|
Term
Glucocorticoids (functions) |
|
Definition
- protect glucose-dependent functions (enhance carbohydrate metabolism)
- promote lipolysis
- enhance vascular reactivity to vasoactive substances
- decrease synthesis of vasodilators
- suppress the HPA axis (decrease ACTH, TSH, GH, FSH)
|
|
|
Term
Glucocorticoids (examples) |
|
Definition
Prednisone Prednisolone Hydrocortisone Beclomethasone Fluticasone |
|
|
Term
Glucocorticoids (function, uses) |
|
Definition
bind glucocorticoid receptor (glucocortcoid response element, GRE) to alter transcription patterns anti-inflammatory; immunosuppressive; inhibit production of arachidonic acid metabolites, cytokine production and release, acute phase reactants; prevent and reverse increased vascular permeability |
|
|
Term
| How do glucocorticoids inhibit production of arachidonic acid metabolites? |
|
Definition
induce lipocortin - inhibits phospholipase A2 inhibit transcription of COX |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
Glucocorticoids (adverse side effects) |
|
Definition
- disturbance in fluid/electrolyte balance
- hypertension
- hyperglycemia
- CNS effects (varied)
- susceptibility to infection
- Cushings syndrome symptoms
- growth retardation (children)
- delayed wound healing
- skin thinning
- muscle wasting
|
|
|
Term
| What are the symptoms associated with Cushings syndrome? |
|
Definition
| weight gain, muscle wasting, diabetes, alteration in fat distribution |
|
|
Term
| How do glucocorticoids cause delayed wound healing and thinning of skin? |
|
Definition
| decreased collagen synthesis |
|
|
Term
| What are the symptoms associated with withdrawal from glucocorticoids? |
|
Definition
flare-up of underlying disease acute adrenal insufficiency |
|
|
Term
Tumor Necrosis Factor-α (TNF-α) |
|
Definition
- pro-inflammatory cytokine
- activates NFκB
- activates MAP kinase
- stimulates acute phase response
- attracts neutrophils
- stimulates phagocytosis by macrophages
changes in signaling, proliferation, differentiation, apoptosis |
|
|
Term
|
Definition
TNFR1, p55/60 - widely expressed TNFR2, p75/80 - soluble, circulates, expressed primarily on immune cells |
|
|
Term
|
Definition
- mimic the action of TNFR2, p75
- binds TNF with high affinity
- side effects: mild upper respiratory, injection site irritation
|
|
|
Term
|
Definition
- monoclonal antibodies (mab) that bind TNF
- adalimumab - human origin
- infliximab - chimeric (1/4 mouse origin)
|
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
| anti-inflammatory cytokine |
|
|
Term
|
Definition
| anti-inflammatory cytokine |
|
|
Term
|
Definition
- anti-inflammatory
- inhibits dihydro-orotate dehydrogenase
- inhibits pyrimidine synthesis
- long t1/2: enterohepatic cycling
- side effects: liver toxicity, 20% loss of BW
|
|
|
Term
|
Definition
anti-inflammatory (unknown mechanism) |
|
|
Term
|
Definition
- prodrug, anti-inflammatory
- metabolized to 6-mercaptopurine (drug)
- inhibits synthesis of purines
|
|
|
Term
Intercellular adhesion molecule-1 (ICAM-1) |
|
Definition
- anti-inflammatory
- integrin family
|
|
|
Term
|
Definition
- Anti-IgE (anti-inflammatory)
- inhibits immune response to allergens
|
|
|
Term
Glatiramer acetate (fr. Copolymer 1) |
|
Definition
- simulates myelin basic protein
- binds MHC II to compete for presentation with myelin antigen
- used to treat MS (multiple sclerosis)
|
|
|
Term
|
Definition
- endogenous cyclic neuropeptide
- bind immune cells
- used to treat experimental colitis
|
|
|
Term
|
Definition
- recombinant, monoclonal Ab to CD11a (neutrophil integrin)
|
|
|
Term
Abatacept Belatacept (CTLA4Ig) |
|
Definition
- CD28 costimulus antagonist
- binds CD80 and CD86
- prevents T cell activation
- treatment of rheumatoid arthritis
|
|
|
Term
|
Definition
| hyperuricemia resulting in monosodium urate deposition in tissues, particularly joints and kidneys |
|
|
Term
|
Definition
- anti-gout
- inhibits migration and activation of leukocytes
- binds tubulin - interferes with mitotic spindles
|
|
|
Term
|
Definition
- anti-gout
- inhibition of xanthine oxidase (uric acid synthesis)
|
|
|
Term
Urucosuric Agents (examples) |
|
Definition
|
|
Term
Uricosuric Agents (function, uses) |
|
Definition
- inhibit organic anion transporter
- decreased reabsorption of uric acid
- ineffective in presence of salicylates
- anti-gout
|
|
|
