NSAIDS Flashcards
common uses for NSAIDS
acute and chronic pain conditions
cancer-associated pain syndromes
treatment of dysmenorrhea
prevention of thrombosis
example of carboxylic acid
acetylated: ASA
nonacetylated: sodium salicylate, salicylamide, difunisal
examples of acetic acids
indomethicin, sulindac, tolmetin
examples of proprionic acids
ibuprofen, naproxen, COX 2 inhibitors
examples of enolic acids
phenylbutazone, piroxicam
examples of pyrrolopyrrole
ketorolac
common therapuetic actions of NSAIDS
analgesic, antiinflammatory, antipyretic, platelet inhibitory effects
MOA of COX inhibition
resulting in decrease in peripheral synthesis of prostaglandins, inhibition of prostaglandin synthesis decreases inflammatory response to surgical trauma, thus decreases peripheral nocioception and pain perception
Two forms of COX
COX-1 is present in all tissues
COX-2 inhibitor-specific dugs reduced likelihood of GI toxicity. Is produced primarily at the site of inflammation
NSAID pharmacokinetics
- well absorbed from the GI tract
- low first pass hepatic extraction
- highly bound (>95%) to plasma albumin
- exhibit small volumes of distribution
- most are weakly acidic. with pK of 3-5
NSAID adverse reactions
dyspepsia, renal problems, skin reactions, CNS issues, inhibition of platelet aggregation
rare NSAID reactions
blood dyscrasias, erythema, uticaria, pneumonitis, aseptic meningitis, aplastic anemia
NSAIDS and gastric acid
prostaglandins go to the paraietal cells and block gastric acid production. If COX is blocked so is prostaglandins, so acid will keep building up causing dyspepsia
NSAID and renal
rarely have effects on renal function in healthy individuals.
Renal toxicity can occur, which is likely due to NSAID induced inhibition of prostaglandin synthesis, which inhibits the compensatory mechanism response for renal medullary ischemia.
What NSAID can be prescribed with absolute safety with respect to renal effects
ASA
NSAIDS and HTN
prostaglandins modulate systemic BP by effects on vascular tone in arteriolar smooth muscle and control of extracellular fluid volume.
Prostaglandins counteract response to vasoconstrictor hormones and can influence sodium balance
NSAIDS may interfere with the pharmacologic control of HTN
Usually clinically insignificant
NSAIDS and coags
due to the reversable inhibition of COX NSAIDS inhibit platelet aggregation, lasts about 5 elimination half times (24-96hrs)
Increasing period use, especially ketorolac has sparked debates among surgeons regarding postop bleeding…
conversely- useful after microvascular surgery
ASA and coags
ASA induces irreversible inactivation of platelet COX
NSAIDS and aseptic meningitis
may follow systemic drug administration especially ibuprofen and H2 receptor agonists
Syndrome is greater in females with underlying autoimmune or collagen vascular disease.
S/S appear within hours but may delay for weeks
Most patietns recover fully when drug is discontinued
Fever is common
Other usual features of meningitis, periorbital edema, conjunctivitis, hypotension, parotitis, fatigue, and seizure
NSAIDS and drug reactions
elderly patients are at greatest risk:
most common- oral anticoags and NSAIDS= increased risk of GI hemorrhage
Potassium sparing diuratics + NSAIDS= increased risk of hyperkalemia
NSAID induced decrease in renal function may interfere with clearance of:
digoxin, lithium, amoniglycoside antibiotics
NSAIDs may interfere with the antihypertensive actions of
beta blockers, diuretics, and ACEI
Periop considerations of NSAIDS
decrease postop pain and requirements for opioids
adjuvants with neuroaxial opioids
IV is better than IM
exhibit ceiling effect when used for post op pain
ASA
a salicylate that produces analgesia through its ability to irreversibly acetylate the COX enzyme, leading to a decrease in the synthesis and release of prostaglandins
The leukotriene pathway remains intact in the presence of ASA.
ASA does OT interact with opioid receptors.
And has LITTLE effect on release of histamine or serotonin.
ASA pharmacokinetics
Rapidly absorbed from the small intestine
Alkalinization of urine may increase urinary excretion, requiring larger doses to achieve plasma concentration.
Buffered effervescent preparations undergo a more rapid absorption and achieve higher plasma concentrations with less GI irritation.
Is ASA a weak acid or weak base?
Weak acid. pKa 3.5
ASA clearance
After absoprtion into systemic circulation, ASA is rapidly hydrolyzed in the liver to salicylic acid.
Metabolism occurs in the liver where it conjugates with glycine to form salicylic acid
Renal excretion of free s.a. is highly variable from up to 85% of alkaline to as low as 5% in acidic
Plasma concentrations increase in presence of renal dysfunction.
Elimination half time is 2/3 hours.
Clinical uses of ASA
A) analgesic for symptomatic relief of low-intensity pain associated with: HA and arthritis
B) Antipyretic
C) Anti-platelet- mainstay therapy/prevention of MI and angina and some ischemic strokes.
ASA side effects
GI upset, hemorrhagic events, easy bruising, melena, epistaxis, CNS stim, hepatic and renal dysfunction, metabolic alterations, uterine effects, allergic rxn
how does ASA increase bleeding time
induces functional defect in platelets that is clinically detectable as prolonged bleeding time.
prevention of the formation of thromboxane, platelets are sensitive to small doses.
irreversible, lasts the lifespan of the platelet.
Avoid is ASA in patients with…
severe hepatic dysfunction, vit K deficiency, hypoprothrombinemia, hemophelia
ASA and CNS stim
excessive dosing of ASA may produce:
- hyperventilation due to direct stim of medullary vent center
- seizures
- tinnitus
- hyperthermia and dehydration may be the life threatening result of salicylate overdose
- metabolic and resp acidosis
ASA hepatic dysfunction
salicylates can be associated with increased plasma concentrations of transminase enzymes, indicating hepatic damage is usually reversible
ASA Renal Dysfunction
chronic use of ASA has not been shown to increase the incidence of ESRD
ASA and metabolic alterations
large doses of salicylates may cause hyperglycemia and glycosuria and may deplete liver and skeletal muscle glycogen
Salicylates decrease lipogenisis by partially blocking incorporation of free fatty acids
ASA and uterine effects
prolongation of labor by salicylates may reflect loss of uterotropic effects of prostaglandins
ASA use is notmally d/c’d before anticipated time of delivery to avoid the potential of postpartum hemorrhage and prolonged labor
ASA allergic rxn
rare and life threatening
vasomotor rhinitis, laryngeal edema, bronchoconstriction, CV collapse
ASA induced asthma
occurs in 8-20% of al asthmatic adults
-greater incidence with rhinosinitus and nasal polyps
Occurs within an hour on ingestion
-life threatening bronchospasm and hypotension
Cross sensitivity between ASA and other NSAIDS must be considered with pts with asthma
Not an allergy- response is not immunologic
Acetaminophen
alternative to ASA -analgesic -antipyretic Especially in patients where salicylates are not recommended -peptic ulcer disease -prolongation of bleeding time
Acetaminophen Pharmacokinetics
nearly complete after oral administration
-no significan binding to serum protiens
Converted by conjugation and hydroxylation in the liver to inactive metabolites
-only small amount of drug excreted unchanged
Acetaminophen side effects
reduction consumption could lower incidence of ESRD 8-10%
Hepatic necrosis and death may accompany a single dose of acetaminophen of >15g
indomethacin
methylated inderole derivative
-analgesic, antipyretic, an anti-inflammatory
MOST potent inhibitor of COX known
useful management of arthritis
drug of choice for treatment of ankylosing spondylitis
Single dose controls cardiac failure in neonates with PDA
Indomethacin side effects
severe adverse effects limit the usefulness
- GI upset and frontal HA
- inhibition of platelet aggregation
- allergic rxn and cross sensitivity with salicylates
- LFTs may become abnormal
- preexisting renal disease patients may experience exacerbation
- neutropenia, thrombocytopenia, and aplastic anemia are rare
Propionic acid derivatives
Ibuprofen, naproxen,
-prominent analgesic, antipyretic and anti-inflammatory agents
-useful in treating various form of arthritis
NAPROXEN has linger elimination half life
side effects of propionic acids
GI and mucosal ulcerations are less than with salicylates
platelet function is altered but varies with specific drug
assume a hypersensitive to salicylates may also be allergic to propionic acids derivatives
what propioic acid is most associated with adverse renal effects?
fenoprofen
side effects with warfarin of propionic acids
extensive plasma protein binding to albumin, must decrease dose of warfarin
ibuprofen problem
hematopoietic suppression characterized by agranulocytosis and bone marrow granulocytic aplasia associated with chronic use of ibuprofen
Ketorolac
Potent analgesic but only moderate anti-inflammatory activity IM or IV
- potentiates the anti-nocioceptive actions of opioids
- exhibit ceiling effect with respect to post op analgesia
- absence of ventilatory or CV depression, little or no effect on biliary tract dynamics
Ketorolac dose
30mg= 10mg MSO4 or 100mg Meperidine
Ketorolac side effects
inhibits platelet thromboxane production and platelet aggregation
bleeding time may be increased
increased post op blood loss must be considered and discussed
Bronchospasm may occur in patient with nasal polyps, asthma, and ASA sensitivity
Cross tolerance between ASA and olther NSAIDS occur regularly
Gabapentin (neurontin)
originally for anticonvulsant purposes
actual MOA unknown, but believed to act on N type voltage gated calcium channels in the CNS
-Many uses including neuropathic pain
-Has undergone scrutiny lately for marketing it’s off label uses
-most common side effects are dizziness and drowsiness
little to no abuse potential.
Pregabalin (Lyrica)
originally for anticonvulsant purposes
- actual MOA unknown but believed to act on N type voltage gated channels in the CNS
- many uses including neuropathic pain
- little or no abuse potential but has been labeled V by FDA
- most common side effects: drowsiness, dizziness
