Module 3: NSAIDs Flashcards
What are some common NSAIDs?
Ibuprofen (Advil)
Diclofenac (Voltaren)
Naproxen (Aleve)
Aspiring (ASA)
Celecoxib (Celebrex)
What are common indications for use of ibuprofen?
Management of inflammatory diseases and rheumatoid disorders.
Mild to moderate pain
Fever
Dysmenorrhea
OA
Off-label: abnormal uterine bleeding, gout
What are common indications for diclofenac?
Ankylosing spondylitis
Dysmenorrhea
Migraine, acute treatment
OA
Mild to moderate pain
Rheumatoid arthritis
Off label - gout
What are common indications for naproxen?
Management of inflammatory conditions
Pain
Fever
Primary dysmenorrhea
Off-label = abnormal uterine bleeding, migraine
What are common indications for ASA?
Mild to moderate pain relief
Headaches
Pain, and fever caused by colds
Muscle aches and pains
Menstrual aches and pains
Menstrual pain
Toothache pain
Vascular indications
Off-label = arterial and venous thrombosis prevention, pericarditis, PAD, polycythemia vera, preeclampsia
What are common indications for celecoxib?
Anti-inflammatory effects
Dysmenorrhea
Idiopathic juvenile arthritis
Migraine - acute treatment
OA
Acute pain
Off label - gout
What are the clinical outcomes/ goals of treatment for NSAID use?
Pain relief
Inflammation reduction
Improved functionality
Fever reduction
Minimizing opioid use
Describe the MOA of NSAIDs.
NSAIDs block the conversion of arachidonic acid to prostacyclins, prostaglandins and thromboxane A2 through inhibition of the Cyclooxygenase (COX-1 and COX-2) enzymes.
COX 1 & 2 are responsible for prostacyclins and prostaglinds.
COX 1 are responsible for thromboxane A2
What is the role of prostacyclins and how they are produced?
COX 1&2 convert arachidonic acid.
Inhibit platelet aggregation
vasodilation
What is the role of prostaglandins and how are they produced?
COX 1&2 convert arachidonic acid.
Hyperalgesia (pain)
Vasodilation
What is the role of thromboxane A2 and how are they produced?
COX 1 conversion of arachidonic acid.
Vasoconstriction
Stimulate platelet aggregation.
What are pharmacokinetic considerations of NSAIDs?
A: GI tract
D: Plasma Albumin
M: Varies from P450 - CYP 2C9, CYP 2C8, CYP3A4, CYP 2Cp, CYP 1A2, CYP 2C19
E: kidneys mostly
Onset: 30-60 mins. 5 mins for ASA. Within 60 for Celecoxib.
Peak: 1-2 hours for ibuprofen and diclofenac, 2-4 for naproxen, 15-120 mins for Aspirin, 3 hours for celecoxib
Duration: Ibuprofen 4-6hrs, Diclofenac 6-8hr, Naproxen 8-12hr, Aspirin 1-4 hr, celecoxib 8-12.
What are special prescribing considerations of NSAIDs with comorbidities?
GI risks (ulcers, bleeding and perforation)
CV (MI, CVA)
Renal function
Hepatic considerations
CNS effects (psychosis, tinnitus, aseptic meningitis)
Respiratory risks (asthma)
What are reproductive, pregnancy and lactation considerations with NSAIDs?
Reproductive:
May delay or prevent rupture of ovarian follicles
Can be continued in patients with rheumatic and musculoskeletal diseases who are planning to father children.
Pregnancy: Use of NSAIDs other than low-dose aspirin for more than 48 hours can cause in utero constriction of the ductus arteriosus as early as 24 weeks gestation, most common after 31-32 weeks.
After 20 weeks, NSADs also have effects on the fetal kidneys that lead to oligohydramnios (decreased amniotic fluid), typically after 48 hours of therapy.
Close to conception - can increase chance of miscarriage
Non-closure of the ductus arteriosus postnatally
Breastfeeding:
Present in breast milk
What are pediatric considerations for NSAIDs?
Dosage adjustment - weight based
age specific information
GI risks
Renal functions
Hepatic considerations
Growth and development
avoid aspiring (<12 = risk of Reye’s syndrome)
Education for caregivers (do not alternate ibuprofen and acetaminophen)
What are prescribing considerations for the older adult and NSAIDs?
GI risks
CV risks
Renal function
Hepatic function
polypharmacy
lowest effective dose
Monitoring - renal and hepatic, BP
What are common side effects to NSAIDs?
GI: stomach pain, nausea, vomiting, heartburn, indigestion, diarrhea, and ulcers
Headaches, dizziness, drowsiness
Fluid retention - swelling in ankles, sudden weight gain and decreased hearing
high BP
allergic reactions
Skin: topical-allergic dermatitis, dryness and scaling
Liver: elevated enzymes, jaundice, inflammation of the liver
Kidney: blood in urine, passing less urine, kidney damage or infection
What are some significant side effects to NSAIDs?
GI - ulcers, bleeding and perforation
CV - MI, CVA
Renal - AKI
Hepatic - decreased function
allergic reactions and asthma
increased bleeding tendency
CNS - headaches, dizziness, tinitus
What are significant drug interactions with ibuprofen?
Anti-inflammatory meds
Blood thinners:
warfarin
apixaban
rivaroxaban
clopidogrel
ticagrelor
Lithium
Methotrexate
Corticosteriods
Alchohol
What are significant drug interactions with diclofenac/naproxen?
anti-inflammatory drugs
Aspirin
Anti-thrombotics = anticoagulants and antiplatelet
BP meds
Antidepressants - SSRIs
Litium
Methotrexate
What are significant drug interactions with aspirin?
NSAIDs
Steroids
Anticoags
SSRI’s
BP meds - ACE inhibitors, diuretics
Phenytoin
Other meds containing aspirin
What are significant drug interactions with celecoxib?
Blood thinners and antiplatelets
Diuretics - furosemide and hydrochlorothiazide
Corticosteroids - prednisone and dexamethasone
SSRI’s
Lithium
Methotrexate
Digoxin
NSAIDs
Amiodarone
Amitriptyline
What are some contraindications and cautions with NSAIDs?
Allergy to NSAIDs, salicylates, sulfonamides
GI - peptic ulcers, known GI bleeding
HTN
CV risks - MI, CVA
Impaired renal function
Liver disease
Pregnancy and lactation
Older adults
Pediatrics
What are the adverse cardiovascular effects of NSAIDs
Cardiovascular death, MI, stroke
Others: HF, HTN, Afib, venous thromboembolism.
What is the mechanism for NSAID related cardiovascular events?
Likely related to COX 2 inhibition which is associated with prostaglandin I2 (PGI2 or prostacyclin) production by vascular endothelium with little or no inhibition of prothrombotic platelet thromboxane A2 production.
The reduction in prostacyclin activity could predispose to endothelial injury.
Prostaglandin G2/H2 convert to Thromboxane A2 and Prostacyclin. What are the functions of each?
Thromboxane A2:
induce platelet aggregation
Potent vasoconstrictor
Induce vascular smooth muscle cell proliferation
proatherogenic (plaque build up)
Prostacyclin:
Inhibits platelet aggregation
Induces vasodliation
Inhibits vascular smooth muscle cell proliferation
antiahterogenic
Gut protection
renal blood flow regulation.
Identify which NSAIDs effect COX-1, COX-2 or both.
Ibuprofen - both
Diclofenac - both
Naproxen - both
Aspirin low dose - COX-1
Aspirin high dose COX-2
Celecoxib mostly COX-2
