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66 Cards in this Set
- Front
- Back
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drug for ductus arteriosis closing and prolong gestation
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indomethacin
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PGE1 analog that prevents GI damage
NSAID + this drug found in combos |
misoprostol
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COX 2 selective agents or chronic high doses of non-selective drugs can cause what side effects
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cardiovascular
MI, stroke, thrombosis |
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NSAIDS have drug interactions with which 4 drugs
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anticoagulants - warfarin
ethanol - increase GI irritation ACE inhibitors - reduces their effects sulfonylureas, methotrexate - compete for protein binding |
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Salicylates
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aspirin, methyl salicylate
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acetic acid derivatives
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indomethacin, ketorolac, sulindac, diclofenac
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propionic acid derivatives
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ibuprofen, naproxan, oxaprozin, ketoprofen
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oxicam
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piroxicam
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coxib
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celecoxib
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only IRREVERSIBLE binding NSAID and its mechanism of action
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aspirin (acetylsalicylic acid)
irreversibly inhibits COX 1 and COX 2 through covalent modifications |
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salicylate absorption
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oral (stomach and upper small intestines, passive diffusion, ion trapping affect)
topical (rapid from in tact skin) |
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salicylate metabolism
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plasma and liver esterases
free salicylic acid conjugates |
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major conjugate/excreted metabolite of salicylates
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salicyluric acid
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salicylate excretion primarily through what?
what metabolites? |
urine
salicyluric acid, glucuronides, free salicylic acid |
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excretion kinetics based on what?
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dose-dependent!!
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low dose aspirin
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first order kinetics
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high dose aspirin
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saturation kinetics
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what else is excretion kinetics based on
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pH dependent
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form in high it must be in to be excreted?
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ionized
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for normal urine at 5.4 and plasma 7.4
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ratio = 100
salicylate is reabsorbed |
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urine pH at 8.4 (alkaline) ratio?
excretion increases or decreases? |
ratio = 0.1
salicylate excretion INCREASES |
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aspirin pharmacology 4 things it does
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alleviates mild to moderate pain
reduces fever reduces inflammation - OA, RA prolongs bleeding time - prophylaxis of stoke, MI (very low dose 75-100 mg/d) |
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methyl salicylate used for?
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ONLY EXTERNALLY as counter-irritant
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less potent then aspirin
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sodium salicylate
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NOT converted ot salicylic acid in vivo
weak anti-pyretic fewer anti-platelet and GI effect POTENT anelgesic and antiinflammatory NO auditory side effects |
diflunisal
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salicylate side effects
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produces gastric bleeding (ion trapping effect)
stimulates respiration (directly and indirectly) changes acid base balance |
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how does salicylate change acid base balance
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respiratory alkalosis
increased HCO3 excretion alkalosis compensated |
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it has drug interactions with what 3 groups of drugs?
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uricosuric agents (probenecid)
anticoagulants - warfarin other protein bound drugs |
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what dose does salicylate interfere with uricosuric agents?
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LOW doses it blocks urate excretion but at HIGH doses it is uricosuric
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other protein bound drugs?
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warfarin
methotrexate valproic acid thyroid hormone |
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contraindications
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hypersensitivity to other NSAIDS
ulcer asthma rhinitis bleeding disorders viral infections in children (Reye's) pregnancy (3rd trimester) |
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use with caution in pts with?
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heavy EtOH use
renal dysfunction or failure severe hepatic failure 1-2 weeks prior to surgery |
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at what concentration does salicylate start causing mild complications/intoxication
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50mg/dL
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what is salicylate at 0-10mg/dL good for?
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analgesia
antipyretic antiplatelet |
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what is it good for at 10-<50 mg/dL
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anti-inflammatory
uricosuric RA |
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acetic acid derivative
reversible non-specific COX inhibitor inactive metabolites HIGH side effects |
indomethacin
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uses for indomethacin
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closure of ductus arteriosus
arthritis acute gout |
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acetic acid derivative
SHORT TERM USE ONLY - 5 days used in post op pain and ocular solution good analgesic, poor antiinflammatory |
Ketorolac
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acetic acid derivative
prodrug - active metabolites t1/2 of active metabolites = 18 hrs less potent and fewer side effects than indomethacin |
Sulindac
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uses for sulindac
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RA, OA, AS, bursitis, tendonitis, acute gout pain
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acetic acid derivative
MORE potent than indomethacin SELECTIVE COX 2 inhibition t1/2 = 1-2 hrs |
Diclofenac
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uses for Diclofenac
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RA, OA, AS, acute pain, migraine, PMS
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propionic acid derivatives
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Non-selective COX inhibition
better tolerated than aspirin or indomethacin DO NOT alter effects of oral hypoglycemic drugs or warfarin |
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4 propionic acid derivative drugs
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1. ibuprofen (2-4 hrs)
2. naproxen (14 hrs) 3. ketoprofen (2-4 hrs) 4. oxaprozin (40-60 hrs) |
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what may these interfere with?
what can be done to prevent this? |
anti platelet activity of low dose aspirin (see for cardio protective effects)
separate doses in time - take at different times |
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OXICAM
inhibits activation of neutrophils t1/2 = 50 hours EXTENSIVE side effects used for RA and OA CHRONIC LONG TERM PAIN |
Piroxicam
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SELECTIVE COX 2 inhibition
fewer GI side effects, and on platelet function MAY PRECIPITATE CV events not first choice drugs - cost used in RA, OA, AS, PM |
coxibs
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coxib drug
teratogenetic effect CV and GI side effects contraindicated after bypass sx t1/2 = 11 hrs |
celecoxib
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celecoxib is metabolized by what?
it inhibits what? |
CYP2C9
CYP2D6 |
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analgesic (equal to aspirin), antipyretic (due to COX inhibition in the brain)
POOR antiinflammatory, antiplatelet, and GI effects |
APAP
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mechanisms of analgesic action of APAP is via what?
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parent compound
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MOA is through what 2 things?
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1. activation of opioid/5-HT systems
2. weak inhibitor of COX activity in the CNS |
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active metabolite of APAP in the brain
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AM404
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MOA of AM404 in the brain (3)
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1. potentiation of cannabinoid/vanilloid tone in CNS
2. via descending 5-HT system to spinal cord 3. weak COX inhibitor in brain |
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AM404 inhibits reuptake of?
endogenous or exogenous fatty acid amide? agonist or antagonist of vanilloid receptors? what is the vanilloid receptor? |
anandamide (endocannabinoid)
endogenous agonist TRPV1 |
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most common cause of acute liver failure in USA?
what percentage of ALF does it cause? |
APAP
50% |
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responsible for more ER visits than any other drug?
can it cause toxicity at therapeutic doses? |
APAP
YES |
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toxic metabolite of APAP?
what does it cause |
NAPQ1
hepatic necrosis |
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NAPQ1 causes this by?
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1. depletes hepatic glutathione
2. causes necrotic cell death |
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antidote for APAP
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NAC
n-acetylcyteine |
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what is essential for NAC treatment?
when is its effect decreased? |
early Dx (8-10 hrs)
after 10 hours |
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toxic risk best predicted by what 2 things
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dose and time
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APAP is metabolized by what 2 ways
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glucuronide
sulfate |
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DRUG interactions:
drugs metabolized by what? Exs of these drugs? what kind of antagonists? |
CYP450
barbiturates (anticonvulsants) Vit K (warfarin) |
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what increases risk of hepatic toxicity?
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EtOH
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what herbal supplement?
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St. John's wort
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