Term
| explain how the two main categories of prostaglandins are made |
|
Definition
phospholipid membrane (phosphitadil inositol) is broken by phospholipase A2 into arachidonic acid
arachidonic acid is converted to either 5-lipooxygenase, COX1, or COX2
to be converted to COX2 it needs to be induced by inflammation (unless in brain and kidney where it is constitutive) |
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Term
| what type of receptors do prostaglandins use |
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Definition
| G protein receptors that activate or inhibit adenylyl cyclase and phospholipase C |
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Term
| explain the 5-lipooxygenase pathway and the 3 effects |
|
Definition
5, 12, 15 - HPETE > 5-HETES > leukotriene >>
phagocyte mobilization, change in vascular permeability, inflammation |
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Term
| what are the 3 products of the COX pathway |
|
Definition
prostacyclin (PGI)
prostaglandin (PGE)
thromboxane A2 (TXA2) |
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|
Term
| 3 effects of prostacyclin |
|
Definition
gastric acid secretion
decreased platelet aggregation
maintain renal flow despite vasoconstrictors |
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Term
| 6 effects of prostaglandins |
|
Definition
maintain renal flow despite vasoconstrictors
sensitize nerve endings to bradykinin and histamine causing pain
increase thermoregulatory center in hypothalamus
stimulate stomach mucous
keep PDA open |
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|
Term
| 1 effect of thromboxane A2 |
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Definition
|
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Term
| where do corticosteroids dysrupt the prostaglandin pathway |
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Definition
| stop phospholipase A2 from breaking phosphitadil inositol from phospholipid membrane into arachidonic acid |
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Term
| where do salycylates dysrupt the prostaglanding pathway |
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Definition
| stop COX2 from inducing PGI, PGE, TXA2 |
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Term
| what are the 4 salicylates |
|
Definition
acetylsalicylate (aspirin)
choline Mg trisalicylate
sulfasalazine
diflundail |
|
|
Term
|
Definition
acetylsalicylate - irreversible COX2 blocker
choline Mg trisalicylate - reversible COX2 blocker
sulfasalazine - reversible COX2 blocker
diflundail - reversible COX2 blocker |
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|
Term
| which salicylate is differet, why |
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Definition
| diflundail: does NOT cross BBB (NO antipyretic), does NOT affect uric acid secretion, 3-4x more potent |
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Term
| 10 non-respiratory effects of salicylates |
|
Definition
anti-inflammation (PGE)
decrease pain (PGE)
anti-pyretic (no effect on normal body temp, PGE)
decrease gastric acid (PGI)
decrease stmach mucous (PGE) causes ulcers and hemorrhage
blood thinning (TXA2, PGI) (irreversible lasts life of platelet in aspirin)
closes PDA
vasoconstriction, Na/water retention, and kyperkalemia in renal vessels |
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|
Term
| respiratory effects of normal, high, and toxic doses of salicylates |
|
Definition
normal: stimulates resporatory medulla, uncouples ETC increasing CO2 stimulating respiratory medilla too, leads to hyperventilation and respiratory alkalosis
toxic: supresses respiratory center causing respiratory acidosis and metabolic acidosis (drug is acid) |
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|
Term
|
Definition
gout
RA
rheumatic fever
headache
arthralgia
myalgia
corns, callus, wart (topical)
blood thinner
angina
close PDA (dec PGE)
decrease colon cancer
ulcerative collitis
anti pyretic
analgesic
antiinflammatory |
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|
Term
| how does the dose of salicylates effect the function |
|
Definition
low dose t1/2 3-5h: blood thinner
med dose t1/2 3-5h: anti inflamm
high dose t1/2 15h: zero order kinetics |
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|
Term
| side effects of salicylates 7 |
|
Definition
epigastric distress
N/V
bleeding
metabolic depression
15% have intolerance/hypersensitivity
rye syndrome: aspirin in viral infection in kids causes hepatitis and cerebral edema |
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|
Term
| interactions with salicylates 4 |
|
Definition
antacids: decrease absorption
heparin: hemorrhage
probenecid: decrease excretion (contraindicatedin grot)
prolonged t1/2, effects, toxicity of many drugs |
|
|
Term
| 5 signs of mild salicycate toxicity |
|
Definition
N/V
hyperventilation
headache
confusion
tinnitus |
|
|
Term
| 9 signs of severe salicylate toxicity |
|
Definition
restlessness
delirium
hallucinations
convulsions
dizziness
coma
death
respiratory acidosis
metabolic acidosis |
|
|
Term
| TX or salicylate toxicity 3 |
|
Definition
increase urine pH to help elimination
IV dialysis
fluids |
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|
Term
| proprionic acid derivatives MOA |
|
Definition
|
|
Term
| story of proprionic acid derivatives |
|
Definition
| I bought a flurb producing napping oxen for ketoz profound ox fender |
|
|
Term
| 6 proprionic acid derivatives and their half lives |
|
Definition
ibprofen 2-4h (dose q4-6h)
flubiprofen 2-4h
naproxen 12-24h (dose q12h)
ketoprofen 2-4h
oxaprozin 58h (dose 1x/d)
fenoprofen 2-4h |
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|
Term
|
Definition
GI irritation (bleed is rare)
renal failure
nephritis
nephrotic syndrome
less anti-coagulation effects means less interactions |
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|
Term
|
Definition
| same as ibprofen plys CV effects |
|
|
Term
|
Definition
| some lipooxygenase inhibition (no greater antiinflammatory effect) |
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|
Term
|
Definition
|
|
Term
|
Definition
| val selectively rolfed on his cox |
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|
Term
| 3 COX2 inhibitors and their SE |
|
Definition
celecoxib - sulfa hypersensitivity, don't anticoagulate (COX2 only), GI bleeds
rofecoxib - DC due to CV events
valdecoxib - DC due to SJS |
|
|
Term
|
Definition
RA
osteoarthritis
COX2 depressed in colon cancer and alzheimers disease |
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|
Term
| story of COX1/2 inhibitors |
|
Definition
| so in the back the key tore Dic's fence so now theres a total lack in da mesh |
|
|
Term
|
Definition
sulindac
ketorolac
diclofenac
etodolac
indomethacin |
|
|
Term
|
Definition
related to indomethican
less SE
converted to sulfide |
|
|
Term
|
Definition
potent analgesic
moderate anti inflammatory
chronic/post-op pain, seasonal allergic conjunctivits |
|
|
Term
|
Definition
| formula with misoprostol (PGE-E1) to decrease GI SE, accumulates in synovium |
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|
Term
|
Definition
| large difference between anti-inflamm dose and GI issue dose |
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|
Term
| indomethacin MOA and uses 7 |
|
Definition
potent anti inflammatory used in gout, arthritis, anylosing spondylitis, acute shoulder
tocolytic: supresses contraction in preterm labor
closes PDA |
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|
Term
|
Definition
GI upset
hepatic disease (increases amniotransferases) |
|
|
Term
|
Definition
|
|
Term
|
Definition
| GI upset, frontal headaches, neutropenia, thrombocytopenia, aplastic anemia |
|
|
Term
|
Definition
analgsic, antipyretic, NO anti inflammatory effect
inhibit PGE synthesis in CNS |
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|
Term
| pharmacokinetics of acetaminophen: normal and OD |
|
Definition
significant first pass: conjugated via glucorindation/sulfination
hydroxylated to NAPQI which at normal dose reacts with glutathione but at toxic dose builds up and depletes glutathione and reacts to hepatic sulhydryl and causes necrosis |
|
|
Term
|
Definition
| n-acetyl cysteine sulfhydryl binds NAPQI as antidote |
|
|
Term
|
Definition
| well tolerated at normal doses, no effect on platelets or uric acid |
|
|
Term
|
Definition
analgesic
antipyretic
DOC reye syndrome prevention (fever in kids with viruses, VZV)
DOC gout pt (not reaction with probenicid) |
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