Eicosanoids, NSAIDs, DMARDs Flashcards Preview

Pharmacology > Eicosanoids, NSAIDs, DMARDs > Flashcards

Flashcards in Eicosanoids, NSAIDs, DMARDs Deck (37):

What the hell is a DMARD?

Disease Modifying Anti-Rheumatic Drug


What is the precursor of eicosanoids and where is this released from?

Arachidonic acid, released from membrane via phospholipase A2


What do COX1 / COX2 do?

They catalyze the oxygenation and peroxidation of arachidonic acid


Where are COX1 / COX2 expressed?

COX1: expressed constitutively everywhere, especially in stomach and platelets

COX2: inducible form, present in inflammatory tissues but constitutive in kidney / vascular endothelium


Which COX is the major source of prostanoids in inflammation and cancer?



Which major eicosanoids are vasodilators vs vasoconstrictors?

Vasodilators: PGE2 and PGI2 (prostacyclin)
Vasoconstrictors: TXA2 (thromboxane) - contract SM

Overall, tend to favor causing vasodilation of blood vessels and hypotension


What is the function of prostaglandins in the stomach?

Maintain secretion of mucins and limit pepsin / acid secretion (inhibition of COX1 causes GI distress / ulcer formation)

COX2 is needed to help existing ulcers heal


What is the CNS effect of prostaglandins?

Pyrogenic and sensitizes nerve endings of pain fibers


What does PGE2 do to the uterus?

Causes contraction


What is the most likely explanation of anti-inflammatory effect of COX-inhibitors?

Diminished eicosanoid effects of vasodilation and sensitization of nociceptive nerves


What can be used to treat pulmonary hypertensions?

Prostacyclin and epoprostenol and Iloprost

(PGI2 analogs which are vasodilators)


What is alprostadil used for?

Maintaining patent ductus arterosus during caridac surgery


What is the first prostanoid used for glaucoma?

Latanoprost - long-acting derivative of PGF2alpha, increased corneal aqueous humor outflow


What are lipoxygenases and generally what do the products do? Do NSAIDs inhibit this?

Family of enzymes catalyzing oxygenation of arachadonic acid to hydroperoxides called "Leukotrienes".

Products are chemoattractants for immune cells, which play a role in asthma and inflammatory bowel disease

NO-> NSAIDs are just COX inhibitors


What is the mechanism of action of aspirin?

Inhibits COX1 and COX2, but preferentially COX1 by irreversibly acetylating the active site.


What are the four main effects of aspirin?

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


How is aspirin antithrombotic?

Inhibits the COX1 expressed in platelets, which would primarily be used to synthesize thromboxanes for platelet aggregation.

It has less of an effect on COX2 which is responsible for vasodilating the endothelium

Generally, this increases clotting time and reduces MI risk / anginal attacks


What are two big risks of using aspirin? What are the mechanisms?

1. Gastric irritation, bleeding, and activation of peptic ulcers by inhibition of gastric COX1

2. Precipitation of gouty attacks (due to inhibition of uric acid secretion by kidney)


How does acetaminophen work and why is it not considered an NSAID?

Nonspecific COX inhibitor which is not actually irritating to the stomach (probably because COX2 > COX1)

Analgesic and antipyretic, but not an NSAID because it does not have anti-inflammatory or anti-coagulant effects


What are the mechanisms of action of ibuprofen and naproxen and how do they differ?

Non-selective REVERSIBLE COX inhibitors, probably greater COX2 activity so they have somewhat less GI side effects than aspirin.

Naproxen just has a longer halflife (Aleve)


What are the common issues with ibuprofen use and why should you not take it with low-dose aspirin?

acute renal failure, interstitial nephritis, nephrotic syndrome.

Should not be taken with aspiring because it may ANTAGONIZE the cardioprotection offered by low dose aspirin (Cox-2 inhibition by ibuprofen disallows vasodilation via vascular endothelium)


What are the indications of indomethacin? Why?

1. Gout
2. Ankylosing spondylitis
3. Pericarditis
4. Pleurisy / pleuritis
5. Patent ductus arteriosus

Not used often due to it being VERY powerful


What are the side effects of indomethacin?

Severe gastric effects, thrombocytopenia, aplastic anemia, hyperkalemia (kidneys), coronary artery constriction


What is Celecoxib? Why would it be used?

A reversible COX-2 inhibitor

About as good as non-selective inhibitors, but might be used because of lower incidence of gastric irritation


When is misoprostol used? Why rarely used?

In concurrence with an non-selective NSAID as a synthetic prostaglandin which can prevent gastric ulcers.

Rarely used due to severe diarrhea (like magnesium lul) and cannot be used during pregnancy (induction of labor)


What do all NSAIDs do to the kidneys?

Decrease renal blood flow, cause fluid retention, and may cause hypertension / renal failure


What are DMARDs used?

They suppress the proliferation and activity of lymphocytes and PMNs which reduce the inflammation, joint destruction, and slow the progression of rheumatoid arthritis


What is the first line drug for RA and what is it often used with?

Methrotrexate -> causes thymidine deficiency

Used in combination with Leflunomide (also reduces pyrimidine synthesis, but can cause serious liver disease)


What is the mechanism of action of leflunomide?

Reduction of pyrimidine synthesis by inhibition of dihydroorotate dehydrogenase


Why is hydroxychloroquine useful in rheumatoid arthritis?

It is a basic drug that accumulates in lysosomes of immune cells and phagocytes (like amoeba and protozoans) and inhibits chemotaxis, phagocytosis, and superoxide production of PMNs.


What particular patient populations is hydroxychloroquine useful in?

Useful in pregnant patients since methotrexate, leflunomide and cyclophosphamide are all teratogens

DO NOT USE in G-6-P DH Deficiency


When are TNF inhibitors used for RA?

In moderate to severe disease, since they are more effective than methotrexate in reducing symptoms


What are the three main TNF scavengers / inactivators? Main side effect?

1. Etanercept
2. Imflixima
3. Adalimumab

Side effect is could cause TB if latent


How does etanercept work?

Enbrel - fusion protect which puts the human TNF receptor on the Fc fragment of IgG, works by scavenging TNF


How does abatacept work? When is it used?

Binds CD80 / CD86 on APCs to prevent T-cell activation via CD28

Used when anti-TNF agents are not working


How does Rituximab work? When is it used?

Binds to B-cell receptor CD20 and causes apoptosis. This is expressed from the pre-B cell stage

Used when anti-TNF agents are not working


Can anti-TNF agents be used as a monotherapy, and what do you do if one doesn't work?

They can, but generally better to use in conjunction with methotrexate

If one doesn't work, you can switch to another anti-TNF which may work, or a non-TNF biological agent like abatacept or rituximab