Study your flashcards anywhere!

Download the official Cram app for free >

  • Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off

How to study your flashcards.

Right/Left arrow keys: Navigate between flashcards.right arrow keyleft arrow key

Up/Down arrow keys: Flip the card between the front and back.down keyup key

H key: Show hint (3rd side).h key

A key: Read text to speech.a key


Play button


Play button




Click to flip

37 Cards in this Set

  • Front
  • Back
Dietary linoleic acid is converted to .... which is stored in .... as ....
Dietary linoleic acid is converted to arachidonic acid which is stored in cellular mbrns as:
--phospholipid esters
What is the function of Phospholipase A2?
It cleaves arachidonic acid from the esters.
What activates Phospholipase A2?
- vasoconstrictor agents
- bradykinin
- thrombin
- tissue injury (ex: menses)
- ischemia (ex: MI)
What is the fate of the freed arachidonic acid?
1. reincorporated into esters in the cellular mbrns

2. serves as substrate for cyclooxygenase which forms the cyclic endoperoxides PGG2 and PGH2 which are precursors of all the PGs

3. serves as substrate for 5-lipooxygenase which synthesizes HPETE, which is the leukotriene (LT) precursor
What are the isozymes of the cyclooxygenase enzyme?
COX-1 (PGH synthetase I)

COX-2 (PGH synthetase II)
What are the functions of COX-1?
1. constitutive "house-keeping" enzyme, esp stomach and kidney

2. activity can be induced 2-4x

3. vascular endothelium/smooth muscle, stomach, kidney, platelets
What are the functions of COX-2?
1. an early inducible enzyme is the inflammatory response

2. activity can be induced 10-20x

3. inflammatory cells, i.e. macrophages
What inhibitors are selective for COX-1?
-- Indomethacin and sulindac are relatively selective, reversible COX-1 inhibitors.
What inhibitors are selective for COX-2?
-- Nabumetone is a relatively selective, reversible COX-2 inhibitor

-- Celecoxib and refecoxib are selective, reversible COX-2 inhibitors
What inhibitors are selective for BOTH COX-1 and COX-2?
-- Ibuprofen causes equal reversible inhibition
-- Asprin irreversibly inhibits both isozymes by acetylation of the active site
-- Salicylate reversibly inhibits both
-- NSAIDs block gene expression of both
-- glucocorticoids block gene expression of COX-2 and increases expression of lipocortin which blocks phospholipase A2 from releasing AA
Name the corticosteroids.

-sone, -lone, and -lide
What do corticosteroids do?
1. Activate gene expression for lipocortin which inhibits phospholipase A2, so the release of arachidonic acid is blocked

2. blocks synth of ALL eicosanoids (PGs, LTs)

3. Blocks expression of genes which code for many cmpds (COX-2, PLA2, cytokines, adhesion molecules, and iNOS)
Corticosteroid use?
treatment of many different types of diseases, including:
- allergic reactions
- arthritis
- asthma
- nephrotic syndrome
What do glucocorticoids do?
1. Inhibit CRH release and thus release of ACTH
-- decrease in plasma cortisol and atrophy of adrenal cortex

2. Inhibit TRH release and thus release of TSH
-- decrease in plasma thyroxine and possibility of hypothyroidism

3. Inhibit GnRH release
-- decrease in plasma FSH resulting in amenorrhea in females and azoospermia in males
Name drugs which interfere with leukotriene synthesis or receptor stimulation.
What does ziluteon do?
Inhibits 5-LO to prevent leukotriene synthesis

Can be used to treat asthma.
What does zafirlukast and montelukast do?
They both block receptors for LTC4 and LTD4, a.k.a. slow reacting substance of anaphylaxis (SRS-A)

Can be used to treat asthma
Name the NSAIDS.
What do NSAIDs do?
1. Prevent synth of PGs by inhibiting COX-1 or COX-2
2. All block COX at relatively small doses, but much larger doses are needed to achieve an inflammatory effect
***Since the NSAIDs do not inhib LO, arachidonic acid liberated in the presence of blockade of the COX-1/2 may be shunted to the lipooxygenase pathway for LT synthesis
Medical uses of NSAIDS?
CV diseases
Tx of primary dysmenorrhea
Inhibition of parturition
Closure of patent ductus arteriosus
NSAIDs and antipyresis
1. pyrogens activate circulating monocytes and release tissue macrophages which then release IL-1
2. IL-1 directly stimulates PGE2 synth in the preoptic area of the hypothalamus
3. PGE2 elevates the thermoregulatory "set point"
-- vasoconstriction of skin for heat conservation
-- skeletal m. contraction for incr. heat production
-- secretion epi = tachycardia, piloerection

NSAIDs block COX-1/2 to stop this PGE2 synthesis
NSAIDs and analgesia
- PGs cause hyperalgesia by sensitizing sensory pain fibers to chemical and mechanical stimuli

- NSAIDs exert a peripheral analgesic effect
NSAIDs and inflammation
***remember, needs to be in larger doses to have anti-inflamm effect

- osteoarthritis and RA
- ankylosing spondylitis
- muscle soreness and joint pain from exercise
NSAIDs and CV diseases?
--TXA2 produced by platelets and monocytes strongly enhances platelet aggregation
-- Aspirin IRREVERSIBLY inhibits the platelet COX-1 via acetylation of active site
-- platelets cannot synth new proteins, so COX-1 is inhibited for life of platelet (9-14 days)
-- Acetylation occurs in portal circulation b/c aspirin is converted to salicylate by first-pass hepatic metabolism, and salicylate is a reversible inhibitor of platelet COX-1
TXA2 and unstable angina?
- TXA2 produced by platelets constricts cardiac arterioles and enhances platelet aggregation = prothrombotic

- TXA2 also been implicated as a causative agent in unstable angina (angina at rest) which is characterized by cyclical falls in coronary blood flow resulting from platelet clots

- treatment with aspirin prevents the cyclical ischemia caused by these platelet clots
What is the benefit of a single, daily small dose of aspirin?
1. decreases MI and secondary MI by 50% in patients with unstable angina
2. prevents secondary MI in patients w/ previous MI (prophylactic effect greatest in first few weeks post-MI)
3. decreases fatal and non-fatal MI by 50% in males >50 y.o. who do not have Hx of previous MI
4. reduces stroke and/or death by 40% in males with transient ischemic attacks (TIAs) and reduces frequency of TIAs
5. reduces incidence of stroke in patients w/ chronic atrial fibrillation
NSAIDS and Tx of primary dysmenorrhea?
ibuprofen is extremely effective in preventing or reversing the symptoms of primary dysmenorrhea:
-- uterine cramping by smooth muscle contraction
-- diarrhea by contraction of GI smooth muscle
-- headache due to cerebral vasodilation
-- nausea and vomiting
NSAIDs and inhibition of parturition?
Increase PGs in the amniotic fluid at term potentiate the normal rhythmic contraction that cayse child birth.

Indomethacin is used to inhibit premature labor
NSAIDs and closure of patent ductus arteriosis?
PGs keep ductus arteriosus dilated in utero

Indomethacin is given i.v. to preterm infants when diuretic drugs, digitalis and respiratory support are ineffective in closing the ductus

-- single dose closes ductus in 75% of infants
-- renal dysfxn (40%) and bleeding problems (5-10%) are common S/Es in preterm infants
Adverse effects of NSAIDs?
-- Aspirin "hypersensitivity"
-- Increased blood pressure
-- Decreased renal fxn or salt/water retention
-- GI ulceration and bleeding
-- slow rate of healing bone
Explain aspirin "hypersensitivity."
- Not a true anaphylactic rxn b/c mast cell degranulation is not involved
- usually occurs w/in 3h of drug ingestion
- symptoms: rhinoconjunctivitis, angioedema, urticaria
- symptoms arise from enhances leukotriene synth after inhib of PGsynthetase with aspirin and other NSAIDs
- assoc with nasal polyps and adult onset asthma
- patients with "aspirin sensitivity" will show same adverse rxn when treated with any NSAID except acetominophen
- celecoxib has been reported to cause HS rxn in aspirin-sensitive patients, but incidence may be less than that caused by the non-selective NSAIDs
NSAIDs and increase blood pressure?
-- Both tonic and stimulated synth and release of vasodilatory PGE2 and PGI2(prostacyclin) blunt the vasoconstriction caused by norepi released from the sympathetic nerves which innervated the vascular smooth muscle
-- vascular endothelial cells tonically release the PGs
-- in addition, the vascular smooth muscle (VSM) cells synth and release PGI2 and PGE2 when stim by endogenously released norepi
-- NSAIDs can produce small elevations in bp by allowing full expression of the vasoconstriction caused nby NE
-- patients vary in this response
-- NSAIDs can also produce a partial reversal of the antihypertensive effects of ACE inhibitors, B-adrenoceptor agonists and thiazide diuretic agents
Why do NSAIDs cause salt/water retention?
-- kidneys are net producers of PGEs
--PGEs produce a diuresis by (1)increasing GFR and (2)attenuating the antidiuretic actions of ADH
-- NSAIDs can produce retention by both decreasing RBF and GFR (RBF decreases more so filtration fraction increases) and allowing full expression of ADH
What type of renal dysfxn is caused by NSAIDs?
1. hyperkalemia (from decreased GFR)
2. interstitial nephritis (flank pain, hematuria, and proteinuria)
3. reversible acute renal failure (ARF)

-- incidence of adverse renal effects caused by celecoxib is equal to that of non-selective NSAIDs
NSAIDs and GI ulceration and bleeding?
PGEs maintain integrity of stomach mucosa:
-- inhibit secretion HCL
-- enhance bicarb secretion
-- stim mucus secretion
-- increase mucosal blood flow
-- stim cell growth and repair

**NSAIDs can produce GI ulceration with greates risk in patients above 60 y.o. and patients treated with corticosteroid or w/ prior Hx of GI ulceration
Gastroprotection vs. Cardioprotection
Aspirin and other non-selective NSAIDs provide cardioprotection in high-risk patients b/c they inhib platelet aggregg, but use increases likelihood of gastric erosion, ulceration, and bleeding
-- selective inhibition of COX-2 provides gastroprotection but may actually increase risk of MI b/c platelet aggregg is not inhibited (COX-1 --> TXA2)
--addition of aspirin to therapy with COX-2 inhibitor provides cardioprotection but negates gastroprotective effect of COX-2 inhibitor
-- may be possible to use very small doses aspirin (40mg) with COX-2 inhibitor to provide needed cardioprotection w/o negating the gastroprotection provided by the COX-2 inhibitor
COX-2 inhibitors and orthopedic surgery?
selective COX-2 inhibitors significantly slow rate of healing of fractured bone, so they should not be used for post-op analgesia after orthopedic surgery