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82 Cards in this Set
- Front
- Back
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Histamine is formed from which amino acid?
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from the decarboxylation of L-histidine
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Where is histamine sequestered?
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mainly in the mast cells and basophils, the brain, and the enterochromaffin-like (ECL) cells of the fundus of the stomach
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True or False
Histamine is only active in the bound form. |
FALSE
Histamine is biologically INACTIVE in the bound form. |
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List the histamine receptors and where they are located.
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H1 - sm.m., endothelium, brain
H2 - gastric mucosa, cardiac m., mast cells, brain H3 - presynaptic: brain, myenteric plexus H4 - eosinophils, neutrophils, CD4 T-cells |
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respiratory effect of histamine.
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bronchoconstriction due to H1 stimulation
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CV effect of histamine
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increased contractility
increased HR due to H2 stim. and reflex tachycardia from H1 stim resulting in vasodilator effects on arterioles |
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GI effects of histamine
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smooth muscle contraction due to H1 stim
increased secretions due to H2 stim |
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What is the "triple response" of a histamine reaction.
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sm.m in microcirc --> dilation
endothelial cells of cap. and veins --> extravasation of fluid sensory nerve endings --> pain stim. and flare |
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char. of 1st generation antihistamines
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strong sedative effect related to CNS distribution
duration of action varies due to CNS distribution |
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char. of 2nd generation antihistamines
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metabolized by CYP3A4 system
duration of action varies due to metabolization by CYP3A4 |
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Where are prostaglandins produced?
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in virtually all tissues and in minute quantities
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What is the precursor to prostaglandin synthesis?
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arachidonic acid
(20 carbon fatty acid) |
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Why are prostaglandins referred to as eicosanoids?
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'eicosa' refers to the 20 carbon atoms
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List the groups of eicosanoids with ring structures.
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prostaglandins
thromboxanes prostaglandins these are all synthesized by the cyclooxygenase pathway |
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What is COX-1 responsible for synthesizing?
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the physiologic production of prostaglandins, ie our everyday prostanoids such as those that regulate normal cell function (gastric cytoprotection, vascular homeostasis, platelet aggregation)
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What is COX-2 responsible for synthesizing?
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prostaglandins that occur in sites of disease and inflammation
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Which has a larger substrate binding site, cox-1 or cox-2?
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cox-2
the larger binding site permitted the development of cox-2 selective inhibitors |
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Which is inhibited by glucocorticoids, cox-1 or cox-2?
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cox-2
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What is the lipoxygenase pathway?
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the action of lipoxygenase on arachidonic acid to form 5-HPETE, 12-HPETE and 15-HPETE, which are unstable and converted into the hydroxylated derivatives known as the HETES
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What are the unstable prostaglandins in prostaglandin synthesis and into what are they transformed?
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PGG2 & PGH2
transformed into PGE2, PGI2, PGD2, PGF2 AND TXA2 |
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Which prostaglandin is more predominant in platelets?
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TXA2
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Which prostaglandin is more predominant in vascular endothelium?
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PGI2
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What is the significance of PGE3 in fish oils?
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if ingested in significant amounts, it diminished the proinflammatory production of PGE2 and the generation of TXA2 resulting in an anti-inflammatory and CV benefit
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What is the half-life of prostaglandins?
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one minute
except for PGI2 (5 minutes) and TXA2 (30 seconds) |
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What kind of receptors are associated with prostaglandins?
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G protein coupled receptors
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List the prostaglandin receptors.
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DP, FP, IP, EP and TP
they correlate with the prostaglandin it associates with. i.e. DP to PGD2; FP to PGF2 |
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Actions of PGD2.
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vasodilation
inhibition of platelet aggregation relaxation of GI and uterine muscle bronchoconstrictor |
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Actions of PGF2.
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myometrial contraction
some bronchoconstriction |
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Actions of PGI2
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vasodilation
inhibition of platelet aggregation renin release & natriuresis |
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Actions of PGE2
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on EP1 receptors - contraction of bronchial & GI smooth muscle
on EP2 receptors - bronchodilation, vasodilation, increased intestinal fluid secretion, relaxes GI smooth muscle on EP3 receptors - GI smooth muscle contraction, inhibits gastric acid secretion, increased gastric mucous secretion, inhibits ANS neurotransmitter release |
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Actions of TXA2
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vasoconstriction
platelet aggregation bronchoconstriction |
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Which prostaglandins are released in an acute inflammatory response?
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PGE2 (predominates) & PGI2 are released by local tissues/blood vessels while mast cells release PGD2.
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What do mast cells release?
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PGD2
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True or False
Prostaglandins directly increase the permeability of postcapillary venules resulting in the redness and swelling associated with an acute inflammatory response. |
FALSE
They potentiate the effects of histamine and bradykinin. |
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True or False
The release of prostaglandins during an acute inflammatory response results in pain as a result of the redness and swelling. |
FALSE
They potentiate the effect of bradykinin by sensitizing the afferent C fibers to the effects of the noxious stimuli. |
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What drug is used to maintain the patency of the ductus arteriosus until surgical correction.
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alprostadil (via PGE1)
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Which prostaglandin agonist is used to treat open-angle glaucoma?
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latanoprost
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Which enzyme is responsible for producing leukotrienes?
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5-lipoxygenase
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char. of LTB4
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chemotactic agent for neutrophils and macrophages
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The anti-inflammatory effects of NSAIDS is related to the inhibition of (cox-1/cox-2) _______.
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cox-2
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The unwanted effects of NSAIDS, especially GI, are related to the inhibition of cox-1/cox-2) _______.
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cox-1
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True or False
NSAIDS can effect normal body temperature. |
FALSE
The antipyretic effects of NSAIDS are a result of inhibition of prostaglandin production in the hypothalamus. |
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How does the analgesic effect of NSAIDS work?
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1. they decrease PG production that sensitizes nociceptors to inflammatory mediators like bradykinin
2. decrease PG production in the spinal cord, decreasing transmission from afferent pain fibers. |
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What components of inflammation do NSAIDS reduce?
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vasodilation
edema pain |
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3 main desired effects of NSAIDS
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anti-inflammatory
analgesic antipyretic |
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cox-1 or cox-2
NSAIDS inhibiting this pathway result in a rapid and reversible inhibition. |
COX-1
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NSAIDS inhibiting this pathway result in an irreversible reaction.
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COX-2
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List some unwanted side effects of NSAIDS use.
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GI - dyspepsia, N/V, ulcers
skin rashes reversible renal insufficiency liver disorders bone marrow suppression analgesic associated nephropathy |
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ASA is more selective for cox-1 or cox-2?
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cox-1
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characteristics of ASA.
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cox-1 selective
inhibits thromboxane production in platelets irreversible inhibition of cox-1 changes ratio of prostacyclin to thromboxane |
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What percent of platelets is renewed every 24 hrs? Why is this significant for ASA dosing?
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1/7 or 14% of platelets are renewed every 24hrs.
This is significant in ASA dosing due to the irreversible inhibition of TXA2 prod in platelets requiring DAILY dosing for effectiveness rather that QOD dosing. |
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True or False
NSAIDS can be taken as a preventative measure to reduce CV risk. |
FALSE
ASA has been shown to reduce CV risk by 30% whereas NSAIDS show no reduction in CV risk. |
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If we have to admin both ASA and NSAIDS, which do we give first and why?
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ASA first, then NSAIDS at least 30 min. later b/c NSAIDS block the cox-1 pathway where ASA works.
In the event the ASA is enteric coated, this does not apply. |
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What are the 3 main risks with taking NSAIDS?
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CV - increase risk of bleeding due to inhibition of platelet aggregation
GI - ulcers, bleeding obstructuve strictures renal - sodium and fluid retention, hyperkalemia, ARF, HTN |
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When do we use a cox-2 inhibitor?
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pts at high risk for GI bleed
use lowest effective dose (200mg for OA; 200-400mg for RA; 400mg for pain) avoid in pts with CV disease |
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What are the 2 main prostaglandins synthesized in the kidney?
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PGE2
PGI2 |
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How do NSAIDS adversely effect the kidney?
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via the cox-2 pathway, inhibits the beneficial effects of PGE2 and PGI2 in the kidney
inhibiting PGE2 results in sodium retention, fluid retention, HTN, vasoconstriction inhibiting PGI2 results in hyperkalemia and ARF |
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Which of the following is/are prodrug(s)?
a. diclofenac b. sulindac c. naproxen d. ibuprofen |
b. sulindac
its metabolized in the liver to its active metabolite |
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True or False
It's acceptable to substitute a different NSAID for one which a pt has had a reaction. |
FALSE
There is cross reactivity between ASA and NSAIDS due to a redirection of arachidonic acid metabolism resulting in increased leukotrienes. |
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The majority of NSAIDS are weak acids or weak bases?
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weak acids
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What does it mean when the therapeutic index of a drug is high?
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The higher the TI, the more safe the drug.
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Which NSAID is labeled renal-sparing?
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sulindac
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What is the significance of ketorolac?
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It's the first injectable NSAID for analgesia. Enhanced efficacy due to its injectability.
If used with an opioid, it decreases the required amt of opioid needed for pain relief. |
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Which NSAID requires taking it on an empty stomach?
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fenoprofen
due to absorption problems with the drug |
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What should we be aware of when admin oxicams?
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high incidence of GI toxicity and phototoxic cutaneous eruptions
no longe used in Europe; FDA still approves use for menstrual cramps and short term pain relief in US |
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Name the pyrazoles. What is the problem with pyrazole administration?
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phenylbutazone
oxyphenbutazone SE of aplastic anemia with a 50% mortality rate administration can not exceed 1 week. |
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Indications for celebrex admin.
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osteoarthritis
RA FAP (familial adenomatous polyps) |
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Why is celebrex effective in treating FAP?
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FAP (familial adenomatous polyps) has been shown to express Cox-2, which celebrex blocks as a cox-2 inhibitor
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What is salicylism?
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high dose ASA admin resulting in tinnitus, decreased hearing and vertigo
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List salicylates. How do the others differ from ASA?
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magnesium choline salicylate
sodium salicylate salicylsalicylate they are less efficacious slower onset no ASA hypersensitivity no drug interactions less GI side effects |
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What effects does acetaminophen have?
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antipyretic
analgesic little anti-inflammatory effect |
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What is the active metabolite of acetaminophen and what is its significance?
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N-acetyl-benzoiminoquinone
it is hepatic and renal toxic treated with N-acetylcysteine |
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characteristics of acetaminophen
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very little protein bound
very little drug interactions mild adverse effects (except with OD) |
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What is gout?
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deposition of monosodium urate crystals in joints and soft tissue
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What is 'usually' the first body part affected by gout?
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the big toe
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what is the enzyme responsible for uric acid production?
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xanthine oxidase
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Uric acid is made from what compound(s)?
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purines, which is converted to hypoxanthine
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normal plasma urate level
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4-6 mg/dl
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types of gout patients
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overproducers and underexcretors
90% of pts are underexcretors |
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What drug(s) are used for acute gouty attacks?
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colchicine - it reduces leukocyte migration into joints
NSAIDS |
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What drug(s) are used for chronic gouty attacks?
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probenecid
sulfinpyrazone |
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What drug(s) are used to prevent gouty attacks? How do they work?
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allopurinol - competitive inhibition of xanthine oxidase
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