Pharmacology of non-opiate drugs (Barker) Flashcards
types of NSAIDs classified by chemical structures
salicylates - ___
arylpropionic acids - ___ and ___
arylacetic acids (4)
enolic acids - ___ and ___
- ASA
- ibuprofen, naproxen
- indomethacin, diclofenac, ketorolac, etodolac
- piroxicam, meloxicam
therapeteutic applications of NSAIDs
analgesic
- chronic postsurgical pain
- potentially inhibit ___ healing
- myalgias/arthralgia (sprains and strains)
- __ pain
- dysmenorrhea (specific PGE effect)
anti-inflammatory
- brusitis and tendonitis
- osteoarthritis and rheumatoid arthritic
- ___ and hyperuricemia
___ (fever)
___ for prophylaxis to reduce risk of MI - antiplatelet effect
- bone
- inflammatory
- gout
- antipyretic
- ASA
inflammatory response to injury is painful
rubor, tumor, calor, dolor = ___ , ___ , ___ , and ___
three phases
1) acute: vasodilation = increased ___
2) subacute - infiltration
3) chronic - proliferation
- redness, swelling, heat, pain
- permeability
recruitment of eicosanoids. contribute to inflammatory pain
mediators recruit inflammatory cells - eicosanoids
- ___ acid metabolites
- prostaglandins ( ___ , ___ , pain)
- thromboxanes
- leukotrienes ( ___ )
- cytokines ( ___ )
- arachidonic
- redness, heat, pain
- swelling
- pain
NSAIDs are ___ inhibitors in the ___ acid pathway
COX, arachadonic
ASA, unlike other NSAIDs
ASA
- ___ inhibits COX1 and COX2 by ___
- modifies COX2 activity = produces ___
- duration of effect corresponds to time required for ___ protein synthesis
other NSAIDs
- competitive ( ___ ) inhibitors of COX1 and COX2
- some arylacetic acids also inhibit ___ sythesis, contributing to anti-inflammatory effect - ___ (Indocin) and ___ (Voltaren)
- irreversibly, acetylation
- lipotoxins
- new
- reversible
- leukotriene
- indomethacin
- diclofenac
therapeutic use of ASA as painkiller
- historically, one of the most common and effective agents for analgesica, antipyresis, and anti-inflammatory use
- frequently used prophylactically for ___
- no ___ development to analgesic effects
- risk in treating children with fever of ___ origin - ___ syndrome
- anti-coagulation
- tolerance
- viral, Reye’s
pharmacokinetic properties of ASA/salicylates
absorption
- ___ absorbed
- passive diffusion of unionized acid at gastric pH
- delayed by presence of ___
distribution
- throughout most tissues and fluids
- competes with many drugs for ___ binding sites
metabolism and excretion
- ASA t1/2 15 ___ - hydrolysis at multiple sites
- salicylate t1/2 6-20 ___ - dose dependent conjugation (saturated)
- active secretion and passive reabsorption in renal tubule
- ___ excretion with increased urinary pH (IV bicarb)
- rapidly
- food
- protein
- min
- houts
- increased
clinical features of salicylism/ASA poisoning
mild effects
- vertigo, ___ , hearing impairment
CNS effects (moderate to severe)
- N/V, sweating, fever
- stimulation followed by depression
- selirium, psychosis, coma
- ___ alkalosis (adults) - caused by hyperventilation
- metabolic acidosis (high dose/kids) - ___ of blood pH
treatment (acute medical emergency)
- reduce ___ load
- increase urinary excretion (dextrose, sodium ___ )
- trap in urine pKa of salicylate is 3.0 → ionized in urine → can’t go back
- treat by correcting metabolic imbalance
- tinnitus
- respiratory, lowering
- salicylate
- ## bicarb
___ acids are very commonly prescibed NSAIDs
- all are potent ___ COX inhibitors
- ibuprofen: t1/2 = __ hrs
- naproxen: t 1/2 = __ hrs
better tolerated than ASA
- inter-patient variation in response and adverse effects
arylpropionic
- reversible
- 2
- 14
therapeutic use of arylacetic acid derivatives
diclofenac (Voltaren)
- increased risk of ___ and renal dysfunction with prolonged use
- Arthrotec (diclofenac/misoprostol) for chronic use misoprostol = ___ analog
indomethacin (Indocin)
- one of the most ___ reverisble inhibitors of PG biosynthesis
- ___ incidence and severity of SE long term
- acute gouty arthritis, ankylosing spondylitis
sulindac (Clinoril)
- less toxic derivatie of ___
- still significant dise effects
- rheumatoid arthritis and ankylosing spondylitis
- peptic ulcer
- PGE1
- potent
- high
- indomethacin
pharacology of eolic acids
- used to treat arthritis
- great ___ penetration
- one of the least ___ side effects
- at low doses ___ in COX-2 selective
- ___ t1.2
- meloxicam = ___ hours
- piroxicam = ___ hours
- joint
- GI
- meloxicam
- long
- 20
- 57
adverse effects of NSAIDs
renal function
- inhibition of renal ___synthesis can lead to increased sodium reabsorption, causing peripheral ___
- higher risk with longer t1/2 NSAIDs and long term use
transient ___ of platelet aggregation
- increased risk of ___ (GI)
inhibition of ___ motility
- therapeutic use for delaying preterm labor
GI distress/ulceration
- risk increases with age ( > __ yrs)
- though less than ___ NSAIDs
- risk increases with long-term use
- 20-50% depending on dose and duration - treat with misoprostol (Cytotec) - ___ analog (induce labor)
- PGE2, edema
- inhibition
- bleeding
- uterine
- 65
- salicylate
- PGE1
therapeutic use of acetaminophen
highly effective as an analgesic and ___
- headaches, fever
limited anti-inflammatory activity - not considered an NSAID
advantages compared with NSAIDs
- no ___ toxicity
- no effect in ___ aggregation
- no correlatioin eith Reye’s syndrome
- liver disease patients < __ gr/day is okay
disadvantages compared with NSAIDs
- little clinically useful anti- ___ activity
- acute overdose may lead to fatal ___ necrosis
- mechanism of action is still unclear
antipyretic
- GI
- platelet
- 2
- inflammatory
- hepatic
AE of acetaminophen
___ toxicity, papillary necrosis
- vasocontriction by inhibition of ___
- greater than ASA and NSAIDs
dose-dependent potentially fatal ___ necrosis
- dose limit ___ g/day
- increased risk with high ___ consumption = increase CYPs
- increase in toxic acetaminophen metabolites ( ___ )
- treat with ___ to detoxify
patients unaware that it’s in multiple products
renal
- PGE2
- hepatic
- 4
- EtOH
- NAPQI
- n-acetylcysteine
SE profile of non-selective COX inhibitors drove development of ___ selective inhibitors
non-selective - ASA, acetaminophen, non-salycilate NSAIDs
- stomach ulcers, GI bleeds
selective COX-2 inhibtors
- rofecoxib (Vioxx)
- reduced ___ and GI ___
- withdrawn due to high chance of blood ___ , stroke, and ___
- black box warning for ___ (Celebrex) - used for arthritis
- COX-2
- ulcers, bleeds
- clots, heart attack
- celecoxib
local anesthetic are ___ channel blockers
lidocaine
- local analgesia (dentistry), itch, burn
- 15 min onset, lasts 30-120 min
bupivacaine
- longer lasting (3.5 hrs), epidural anesthesia
benzocaine
- ___ use, oral ulcers, ear pain
- __ have higher allergy risk
Na
- OTC
- esters
overview of calcium channel blockers as possible analgesics
major function = ___ and ___
___ (Neurontin), ___ (Lyrica)
- a2delta - Cav1, 2 selective
- not ___ , not protein bound
- no drug-drug interactions
- t1/2 = 4-8 hours
Ziconotide (Prialt)
- snail toxin (peptide)
- use in opioid intolerant px
levetiracetam (keppra) -well tolerated, may cause mood symptoms
- HR, BP
- gabapentin, pregabalin
- metabolized
