Eicosanoids

This drug should NOT be given with TNF-inhibitors as the incidence of serious infection increase greatly

Abatacept (Orencia)

What NSAID is readily absorbed from the stomach?

Aspirin

What drugs anti rheumatic effects are similar to methotrexate but may also increase the risk of lymphoma

Azathioprine

Where is COX2 found?

Cells involved in inflammation (macrophages), vascular endothelium and renal juxtaglomerular apparatus

What is a humanized, pegylated, Fc-free, monoclonal anti-TNF alpha approved for use in Crohn's disease

Certolizumab (Cimzia)

What are Eicosanoids?

Chemically diverse family of autacoids

PGI and PGE reduce the effects of ADH in the

Collecting duct

LTC4 and LTD4 attract

Eosinophils

What is a fusion protein consisting of human TNF receptor and the Fc fragment of IgG? This recombinant protein also scavenges the TNF

Etanercept (Enbrel)

NSAID's are generally (hydrophobic/hydrophilic) molecules with a carboxylic acid group

Hydrophobic

What drug is also used in the treatment of malaria and ameba infestation?

Hydroxychloroquine

Aspirin overdose is common in children resulting in:

Hyperventilation and respiratory alkalosis, metabolic acidosis, respiratory depression

What drug is a very powerful NSAID that has serious untoward effects including gastric effects, headache thrombocytopenia, anemia and others

Indomethacin

Inhibition of COX1 and COX2 produces palliative relief from

Inflammation

What is a chimeric human mouse monoclonal anti-TNF that also reduces symptoms by inactivating TNF after intravenous injection?

Infliximab (Remicade)

How does Aspirin provide Anti-thrombotic effects?

Irreversibly inhibits platelet COX1 without significant effect on endothelial COX2 increasing clotting time

Why is Acetaminophen not actually an NSAID?

It has weak anti-inflammatory properties

This drug is a monoclonal antibody against IL-17 used against psoriasis

Ixekizumab (Taltz)

PGE and PGI are synthesized and act locally in what organ?

Kidney

In the GI tract _____ is secreted by colonic epithelial cells (high levels in inflammatory bowel disease)

LTB4

What is a chemoattractant for PMN's, eosinophils, and monocytes

LTB4

COX2 selective inhibitors preferentially inhibit COX2 compared to COX1 because the hydrophobic channel of COX2 is _____ (larger/smaller) than COX1

Larger

What drug undergoes hepatic metabolism to an active compound that inhibits dihydroorotate dehydrogenase and can cause diarrhea, hair loss and hepatic damage

Leflunomide

What products are associated with asthma, anaphylactic shock and cardiovascular disease?

Lipoxygenase

Absorbed aspirin is widely distributed and metabolized in what organ?

Liver

Ibuprofen, Naproxen, Fenprofen, Ketoprofen and others are phenylpropionic acid derivatives and are ______ (more/less) potent than aspirin

MORE

What drug has properties similar to aspirin with less gastric effects?

Meclofenamate

What drug is the standard of care for DMARD therapy?

Methotrexate

What drugs reduce inflammation and are analgesic and antipyretic?

NSAID's

In the nervous system, pyrogens induce synthesis of

PGE

Prostaglandins, prostacyclin and thromboxanes are derived from

PGH2

In vascular endothelium the principal product is?

PGI2

What drug is another powerful NSAID with an array of serious untoward effects and is seldom used except in acute gouty attacks

Phenylbutazone

Where is TXA2 (thromboxane) the principal product?

Platelets

What drug is a prodrug; hepatic metabolite undergoes enterohepatic cycling prolonging the duration of action?

Sulindac

What are Autacoids?

Synthesized in response to specific stimuli, act quickly locally, briefly remain active

Biologicals that reduce levels of ____ are more effective than methotrexate in reducing RA symptoms and joint destruction

TNF

What is produced by macrophages and T-lymphocytes in the synovium and causes recruitment of inflammatory cells, angiogenesis and tissue destruction?

TNF (tumor necrosis factor)

This drug is a monoclonal antibody against IL-6 receptors used against RA

Tocilizumab (Actrema)

This drug is a Janus Kinase (JAK) inhibitor used against RA and psoriasis by blunting inflammatory responses

Tofacitinib (Xeljanz)

T/F: All NSAID's (including celecoxib) inhibit renal prostaglandin synthesis, decrease renal blood flow, cause fluid retention and sometimes renal failure

True

In the Uterus, TXA2, PGF2 alpha and low doses of PGE2 cause

Uterine Contraction

PGE and PGI are ________ and increase GFR

Vasodilators

This drug is a monoclonal antibody used against alpha4 beta7 integrin in crowns disease and ulcerative colitis and RA

Vedolizumab (Entyvio)

Metabolism is satiable and elimination of Aspirin is what order?

Zero

Prostaglandins and thromboxanes cause GI smooth muscle to

contract

NSAID's reduce the synthesis of prostaglandins (PG), thromboxanes (TXA) and prostacyclin by inhibiting

cyclooxygenases

Eicosanoids have very _____ (long/short) half lives and are inactivated first by specific enzymes followed by fatty acid oxidation

short

In what organ do PGE2 and PGI2 predominate?

stomach

In platelets COX1 synthesized TXA2 increases the effect of

thrombin

There are 2 forms of cyclooxygenase (COX1 and COX2) that catalyze the same reactions but have different _____

tissue distributions

What drug is a pro-drug and is absorbed and thought to exert the anti-rheumatic effects (used in IBD)

Sulfasalazine

Celecoxib and Valdecoxib are _______ derivatives and have caused allergic reactions in patients who are hypersensitive to them.

Sulfonamide

What are eicosanoids derived from?

Arachidonic acid (4DB)

What are the ASA 4 principal pharmacological effects?

1. Analgesia 2. Antipyresis 3. Anti-inflammation 4. Anti-thrombotic

PMN's, basophils, mast cells, eosinophils and macrophages contain

5-lipoxygenase (5-Lox)

What drug is a non-specific COX inhibitor but not an NSAID

Acetaminophen

What drug is analgesic, antipyretic but has NO anti-inflammatory or anticoagulant effects?

Acetaminophen

What drug is extensively metabolized hepatically

Acetaminophen

Proper treatment with _______ reduces hepatotoxicity from acetaminophen?

Acetylcysteine

How does Aspirin provide Analgesia?

Acts peripherally and centrally in CNS to relieve mild to moderate pain

What is a human antibody that is given subcutaneously and acts like imfliximab?

Adalimumbab (Humira)

What is a recombinant protein that is a competitive antagonist at the IL-1R. A marginally effective drug

Anakinra (Kineret)

Non-selective COX inhibitors are reversible inhibitors but are less useful as

Anticoagulants

How does Aspirin provide Antipyresis?

Blocks pyrogen induced PG synthesis in the HT to lower febrile but NOT basal body temperature

This drug is a monoclonal antibody against IL-17 receptor used against psoriasis

Brodalumab (Siliq)

LTC and LTD have been identified as the Slow reacting substance of anaphylaxis (SRS-A) that is secreted in anaphylaxis and asthma and are powerful

Bronchoconstrictors

A principal limiting factor in ASA use is gastric irritation, bleeding and activation of peptic ulcers. This effect is due to inhibition of gastric

COX1

Aspirin inhibits both COX1 and COX2 but has a significantly higher affinity for which one?

COX1

Inhibition of _____ can cause considerable GI distress

COX1

What 2 molecules catalyze the same two step reaction (oxygenation and per oxidation) to produce the prostaglandin, PGH2?

COX1 & COX2

Celecoxib (Celebrex) is a selective reversible inhibitor of

COX2

In the lung TXA _______ (constrict/relax) bronchiolar and tracheal muscle; prostacyclin and PGE ______ (constrict/relax)

Constrict; Relax

What drug is potent with high incidence of gastric effects?

Diclofenate

What does DMARD's stand for?

Disease Modifying Anti-Rheumatic Drugs

What is a human monoclonal antibody with high affinity anti-TNF alpha?

Golimumab (Simponi)

Aspirin is eliminated by the kidney where it competes with uric acid for secretion in the

Proximal tubule

H2 receptor antagonists (ranitidine) ______ (reduce/promote) NSAID related dyspepsia

Reduce

What do DMARDs do?

Reduce inflammation, joint destruction and slow or stop progress of rheumatoid arthritis

This drug is a chimeric monoclonal antibody that targets the B-cell antigen (CD20) and is given by IV infusion

Rituximab (Rituxan)

Proton pump inhibitors (omeprazole) reduce dyspepsia and ulceration in the _____ (short/long) term

Short

Where is COX1 found?

Stomach, Platelets and many other tissues