ch 57 Flashcards
what cox inhibitor can protect against MI and stroke
only Aspirin
which is good cox?
COX - 1
which is bad COX?
COX-2
what does COX1 do
housekeeping chores
protect gastric mucosa
support renal function
promotes platelet aggregation
What does COX2 do
mediates inflammation sensitizes receptors to painful stimuli mediates fever and perception to pain in brain supports renal function in kidney promotes vasodilation can contribute to colon cancer
where is COX 2 produced
mainly at sites of tissue injury
first generation NSAIDs inhibit
COx 1 and 2
Second gen NSAIDs inhibit
COX2 only
which COX carries an increased risk for MI and stroke
COX2
which COX has adverse effect of renal impairment
COX2
COX 1 & COX 2 inhibitors
Promotion/Prevention of MI and stroke and why
COX1 - protects against MI and stroke secondary to reduced platelet aggregation
COX2 - Promotes MI and stroke secondary to suppressing vasodilation
Drug of choice for rheumatoid arthritis, osteoarthritis and juvenile arthritis
Aspririn
Benefits of ASA
inhibiting COX 2
-reduce inflammation, pain and fever
inhibiting COX1
-protect against MI and ischemic stroke
adverse effects ASA
gastric ulceration, bleeding and renal impairment
from inhibiting COX1
ASA is a ______ inhibitor of __________
ASA is an irreversible inhibitor of cyclooxygenase
NSAIDS are a ______ inhibitor of ________
NSAIDS are a reversible (competitive) inhibitors of cyclooxygenase
ASA metabolism
rapid conversion to salicylic acid (active metabolite)
salicylic acid is extensively bound to
plasma albumin (distributes to all body tissue and fluid including breast milk, fetal tissues and CNS)
used in rheumatic fever, tendinitis and bursitis to suppress inflammation
ASA
ASA is most active in what kind of pain
joint pain
muscle pain
headache
drug of choice for reducing fever in adults
ASA
you cannot give ASA to kids, why
Reye syndrome
ASA will reduce fever but will not lower ____
body temperature or temp that has been elevated in response to physical activity or rise in environmental temps
body temp is regulated by the
hypothothalamus
fever occurs when
the set point of the hypothalamus becomes elevated which causes hypothalamus to increase heat production and decrease heat loss
the set point of the hypothalamus elevation is triggered by
local synthesis of prostaglandins in response to endogenous pyrogens (fever promoting substances_
ASA works on fever
lowers the set point by inhibiting Cox 2 and inhibits pyrogen-induced syntheses of prostaglandins
TXA2
promotes clotting
ASA suppresses platelet aggregation by causing
irreversible inhibition of COX1
COX 1 makes what (platelet aggregation)
TXA2
once a platelet has inhibition of COX1
platelet cannot make TXA2 to promote platelet aggregation for the life of the platelet (body has to make new) - essentially inactivates this
Daily ASA is recommended for pt with history of
ischemic stroke TIA Acute MI Previous MI Chronic stable angina Unstable angina Angioplasty and other revascularization procedures
ASA dose recommended for prevention of cardiovascular disease
75-81mg/day
higher doses offer no greater protection but will increase risk for GI bleeding
ASA decreases risk of ________ cancer due to inhibition of COX ___
colorectal
COX2
side effects ASA
gastric distress heartburn nausea occult GI bleeding (most cases the daily amount is insignificant - with long term use it can produce anemia
gastric ulceration, perforation and bleeding due to increased secretion of acid and pepsin
Decreased production of cytoprotective mucus and bicarbonate
decreased submucosal blood flow
direct irritation of ASA on gastric mucosa
increased risk of gastric ulceration - can occur without preliminary signs
advanced age PUD previous intolerance to ASA or other NSAIDS Cigarette smoking history of alcohol abuse
hemorrhage secondary to gastric ulceration is due to
(hemorrhage due to erosion of stomach wall and suppression of platelet aggregation)
how do we prevent ulcers
PPI (proton pump inhibitor)
it is recommended that pts with gastric ulcer histories be tested for
H.Pylori
taking just 2 (325mg) ASA can double bleeding time for
1 week
ASA is contraindicated in
use in caution in
Bleeding disorders such as hemophilia Vit K deficiency hypoprothrombinemia HTN - increase r/o hemorrhagic stroke - should be 150/90 or preferably lower prior to starting pregnancy in third trimester kids who have chickenpox or influenza infants
caution in older adults
smokers - higher risk for GI ulceration
H.pylori - linked to GI/bleeds
increased risk for renal injury
ASA causes salt and water retention and edema
increased r/o renal injury due to ASA inhibiting cox1 which deprives kidney of prostaglandins needed for normal function
This is for the following:
heart failure -
hepatic cirrhosis - bleeding risk these pt commonly have coagulation disturbances, increased r/o renal injury. . These pt are at increased risk
hypovolemia -
renal dysfunction
can cause an exacerbation (salicylate hypersensitivity)
asthma -
hay fever
chronic urticaria
nasal polyps - risk for bleeding
asthma and nasal polys - at risk for hypersensitivity
history of alcoholism - higher risk of GI ulceration
anticoagulant therapy
ASA should be d/c at least ______prior to surgery
1 week to minimize blood loss
Do you need to stop ASA prior to dental, derm or cataract surgery
no
ASA impairs renal function by inhibiting
COX1 which deprives kidneys of prostaglandins needed for normal function
s/s of renal impairment
reduced urine output
weigh gain despite use of diuretics
rapid rise in serum creatinine and BUN
a syndrome that begins to develop when ASA levels are barely over therapeutic
Salicylism
s/s of Salicylism
tinnitus
sweating
headache
dizziness
if salicylism develops, what do you do?
withhold ASA until symptoms subside
resume ASA but with a lower dose
Tinnitus and ASA
when tinnitus occurs - max acceptable dose has been achieved. but may not be appropriate in older adults who may not develop tinnitus even if levels become toxic
ASA acts on CNS to affect resp
Acts on CNS to stimulate breathing -> increase CO2 loss and causes respiratory alkalosis
in response to resp alkalosis the kidneys
excrete more bicarbonate -> then there is a buildup of acids which produces metabolic acidosis
Ph reflection in salicylate tox
mixed acid base imbalance
characteristic symptoms of Reye
encephalopathy
fatty liver degeneration
epidemiologic connection between Reye syndrome and
child having active influenza or chicken pox
ASA and pregnancy
linked to anemia and postpartum hemorrhage and prolonging labor. Can affect fetus.
ASA and fetus when taken during pregnancy
prostaglandins prevent closure of ductus arteriosus. ASA can block prostaglandin synthesis and may induce closer of the ductus arteriosus.
associated with low birth weight, stillbirth, renal tox, intracranial hemorrhage and death
ASA and breastfeeding
safe
in older adults ASA
contribute to elevated BP
precipitate CHF decompensation
renal failure
ASA drug interactions
Anticoagulants - can intensify effects of Warfarin, heparin and others. Can increase risk of gastric hemorrhage.
Glucocorticoids - both promote gastric ulcers. A PPI or H2RA for prophylaxis
Alcohol - both increase r/o gastric bleeding. Higher if have 3 or more alcoholic drinks every day while using ASA
NSAIDS - can negate ASA benefits. Give ASA 2 hours before other NSAIDS or utilize high dose ASA therapy instead of using in combo
ACE and ARB - can both increase r/o impaired renal function/renal failure. Low dose ASA is fine, but High dose ASA is a problem
Vaccines - ASA and other NSAIDS can blunt the immune response to vaccines. Should not be used routinely to prevent vaccination associated pain and fever
Gastric irritation can be minimized when taking ASA with
taking it with water or food
ASA and Pt/ptt
increases bleeding time without affecting PT/PTT
ASA and gout
competes with uric acid for excretion and can worsen gout
ASA overdose treatment
Activated charcoal
Bicarb
Vent support
NSAIDs and ASA which is irreversible and which is reversible
ASA irreversible
NSAIDS reversible
NSAIDS and cardiovascular
increase risk for thrombotic events
highest cardiovascular risk in NSAIDS
indomethacin
sulindac
meloxicam
NSAIDS should not be used before coronary artery bypass graft surgery (CABG) or for how long after
14 days
what hypersensitivity reaction is linked to ibuprophen
Stevens Johnson syndrome
What is Stevens Johnson syndrome
hypersensitivity reaction
a severe hypersensitivity reaction that causes blistering of the skin and mucous membranes and can result in scarring, blindness, and even death.
Nonacetylated salicylates: Magnesium salicylate, sodium salicylate and salsalate similarities to ASA
inhibit COX1 and COX 2
treat arthritis, moderate pain and fever
GI disturbances
dont give to children with flu or chickenpox - Reye syndrome
does not protect against MI or stroke
avoid in pt with sodium restricted diet (heart failure or HTN)
dont use in renal insufficiency - toxic levels
COX 2 blockers (COXIBS)
suppresses inflammation and pain
somewhat lower risk for GI side effects
can impair renal function ->hypertension and edema
increase risk for MI/stroke
Celecoxib (Celebrex) is for
osteoarthritis RA Juvenile idiopathic arthritis acute pain ankylosing spondylitis dysmenorrhea
what rare genetic disorder can Celecoxib (celebrex) be used
familial adenomatous polyposis - predisposes a development of colorectal cancer
what does Celecoxib (Celebrex) block
selective COX 2 inhibitor
Celecoxib (Celebrex) binds to
plasma proteins
adverse effects Celecoxib (Celebrex)
GI ulceration - lower because it does not block cox 1 which offers GI protective effects - combining with PPI will reduce the possibility
Avoid Celecoxib (Celebrex) in
existing heart disease those who have just undergone CABG surgery HTN Diabetes Dyslipidemia
following are at higher risk for renal impairment HTN EDEMA Heart failure Kidney disease
why is risk of MI and stroke increased in Celecoxib (Celebrex)
it causes vasoconstriction and does not inhibit COX 1 which means platelet aggregation is not suppressed.
what allergy cant have Celecoxib (Celebrex)
sulfa
Celecoxib (Celebrex) in pregnancy
this and other nsaids can cause premature closure of the ductus arteriosus
contraindicated in 3rd trimester
Drug interactions Celecoxib (Celebrex)
warfarin - increased bleeding risk by enhancing anticoagulant effects
may decrease the diuretics effects of furosemide
ACEs decrease antihypertensive effects bc it causes HTN
Lithium - increase levels
Levels of Celecoxib (Celebrex) may be increased by fluconazole (antifungal)
does acetaminophen have antirheumatic actions
no - it does not have antirheumatic or antiinflammatory effects like NSAIDS
does acetaminophen suppress platelet aggregation
no so it does not cause gastric ulceration or decrease renal blood flow
acetaminophen major adverse reaction
severe liver injury with overdose
what is the difference in acetaminophen and ASA
ASA inhibits cyclooxygenase in both CNS and periphery - cox 1 and cox 2
tylenol is only CNS (Cox-2)
what enzyme is required to convert the tylenol to nontoxic metabolites
glutathione - in liver so in therapeutic doses
in overdose your liver runs out of glutathione so it causes severe liver injury
adverse effect of tylenol
daily use connected with HTN
Stevens Johnson Syndrome
TEN (toxic epidermal necrolysis)
AGEP (acute generalized exanthmatous pustulosis)
SJS
TEN
are
medical emergencies and can lead to death
AGEP is characterized
by pustular lesions that predominately affect the upper trunk and body folds - usually resolves within 2 weeks of onset.
stop tylenol, seek medical attention
alcoholics and tylenol
increased risk for liver injury
induces synthesis of P450 containing enzyme -> increasing production of tylenol toxic metabolite
stores of glutathione are depleted in chronic alcoholics
chronic alcoholics have preexisting liver damage makes them less able to tolerate injury from tylenol
can increase risk for both liver and kidney damage
which meds interact with Warfarin
ASA
Tylenol
Celebrex
if you are an alcoholic, you should consume no more than ______ mg/day
3000 instead of 4000
is tylenol useful in treating rheumatic fever
no because it has no antiinflamatory properties
med for tylenol overdose
Mucomyst (acetylcysteine)
principal feature of tylenol overdose is
hepatic necrosis
severe tylenol overdose can progress to
hepatic failure
coma
death
early symptoms of tylenol overdose
n/v/d
sweating
abd pain
How does mucomyst work
substitutes for depleted glutathione to convert the toxic metabolite to the nontoxic
100% effective within 8-10 hours
even when 24 hours later it can help
