Antipyretics, Anti-inflammatory and analgesics Flashcards
What are eicosanoids?
Members of a family of oxygenated products of polyunsaturated long-chain fatty acids
Prostaglandins, Thromboxanes, Leukotrienes
What is arachidonic acid?
Most abundant and important precursor of eicosanoids
Synthesized from linoleic acid
What is the form and function of COX-1?
Constitutive form found in endothelial cells, stomach and kidney
Housekeeping functions, increased stomach mucus
What is the form and function of COX-2?
Inducible by inflammation and cytokines
Immediate early response gene product in inflammatory/immune cells
What is the MoA of Prostanoids?
Paracrine/autocrine
Activate G proteins or PIP metabolism
Major affects are on smooth muscle: vascular, GI, airway, reproductive
What is the use and ADR of Misoprostol?
PGE1 analog
Adjunct to NSAID therapy to reduce ulcer formation
Inhibits gastric acid secretion
Contraindicated in pregnancy
What is the use of Latanoprost?
PGF2a analog
Ophthalmic preparation, used for open angle glaucoma
Increases aqueous humor outflow
What is the use of Alprostadil?
PGE1
Temporarily maintains patent ductus arteriousis in newborns until surgery can be done
Increases pulmonary blood flow, improving blood oxygenation
What does the lipoxygenase pathway produce?
Leukotrienes
What is the function of Leukotriene B4?
Chemotactic agents for PMNs
Can also produce hyperalgesia
What are the functions of the Cysteinyl Leukotrienes (LTC4, D4, and E4)?
Potent bronchoconstrictors
Increase vascular permeability
Components of slow reacting substance of anaphylaxis
What is CysLT1 and its function?
Eicosanoid receptor
Pulmonary inflammation and fibrotic response
What is the MoA for Afirlukast and Montelukast?
Competitive, reversible LTD4 (CysLT1) receptor antagonist
Inhibits LT mediate effects on bronchoconstriction and vascular permeability
What are the uses for Zafirlukast and Montelukast?
Prophylactic treatment for Asthma
Monte - 1yr or older
Zafir - 5yr or older
Allergic Rhinitis
Aspirin sensitivity induced asthma (montelukast only)
What is the dosage for Zafirlukast?
20mg BID
What is the dosage for Montelukast?
10mg for adults or 4mg for children QD
What are the ADRs and interactions of Zafirlukast?
Headache, pharyngitis, increased liver enzymes
Inhibits CYP3A4 and 2C9 (warfarin)
Must be taken 1-2 hrs prior to food
Whats the ADR for Montelukast?
Headacke
What is the MoA of Zileuton?
Inhibitor of 5-lipoxygenase
Inhibits synthesis of leukotrienes
What is the use for Zileuton?
Prophylaxis for asthma in adults/children over 12
What is the dosage for Zileuton?
400-800mg 2-4x daily
What are the drug interactions for zileuton?
Theophylline
Warfarin
Propranolol
What are the ADRs for Zileuton?
Contraindicated in liver disease
Ergot alkaloids contraindicated
Seldom used in USA due to safety
What is the MoA of NSAIDs?
Inhibits cycloxygenases
Non-selective
Aspirin - irreversible inhibitor
What are the common therapeutic actions of aspirin and NSAIDs?
Antipyretics - inhibit PG synthesis in the hypothalamus
Analgesics - reduction of mild to moderate pain associated with inflammation
Anti-inflammatory properties - inhibits localized PG synthesis
What are four common side effects associated with aspirin and tNSAIDs?
Increased risk of GI ulcers and pain
Increased risk of bleeding
Inhibit PG mediated effects in kidney (fluid retention)
Hypersensitivity with aspirin
What are three major drug interactions with NSAIDs?
ACE inhibitors
Glucocorticoids
Warfarin
What is the MoA of aspirin?
Irreversible inhibitor of cyclo-oxygenase
Acetyl salicylate
Acetylates the enzyme
What are the uses for aspirin?
Antipyretic, anti-inflammatory and analgesic agent
*rarely used as anti-inflammatory agent
Analgesic activity at localized area and in brain, does not interact with opioid receptor
What is the analgesic/antipyretic dose of aspirin?
Adults - 325-650mg every 4 hours
2-3hr half life
What is the anti-inflammatory dose for aspirin?
4-6g daily
Half life is 12 hours
What is the fatal dose for aspirin?
10-30g
half life 15-30 hours
What is aspirin’s effect on platelets?
Irreversibly inhibits platelet COX
Low doses can irreversibly inhibit TXA2 production
Prevents platelet aggregation
What are the clinical uses for aspirin?
Low dose - decreases incidence of TIAs, unstable angina, coronary artery thrombosis with MI and thrombosis after CABG
Risk reduction for Preeclampsia
What are the side effects of aspirin?
GI pain, bleeding and ulcers
Variable urate excretion
Reye’s syndrom in children w/ varicella
What is salicylism?
Mild intoxication with aspirin
Characterized by tinnitis, high frequency hearing loss, headache, nausea, dimness of vision
Reversible
What are the propionic acid derivative NSAIDs?
Ibuprogen, Naproxen
What is the MoA of Ibuprogen and naproxen?
Competitive, reversible active-site inhibitors of COX 1 and 2
What are the uses for for Ibuprogen and Naproxen?
Analgesic for mild pain
Antipyretic
Anti-inflammatory - symptoms of RA and osteoarthritis
What are the uses for ibuprofen?
Fever in children
Dysmenorrhea
Acute migrain attacks
RA and osteoarthritis
What are uses for naproxen that ibuprofen can’t be used for?
Acute gout
Tendonitis
Ankylosing spondylitis
What are the ADRs for Naproxen (Aleve)?
Increased risk of stroke/HA with prolonged use
What are the drug interactions with naproxen?
ACE inhibitors
Antacids and Sucralfate (cation chelation)
What are the heteroaryl acetic acid derivative NSAIDs?
Ketorolac
What is the use for the ophthalmic prep of Ketorolac?
Seasonal allergy
Recovery from cataract surgery
What are the other uses for Ketorolac?
Excellent analgesic action
Used for postoperative pain
What are the ADRs for Ketorolac?
GI bleeding
Bleeding
Decreased hepatic function
Lower dose in patients under 110 lbs or elevated creatinine
What are the contraindications for ketorolac?
History of peptic ulcer or GI bleeding
Stop before surgery
Concurrent use with aspirin or NSAID
During labor/delivery or during lactation
What is the phenylacetic acid derivative NSAID?
Diclofenac
What are the uses for diclofenac?
RA, osteoarthritis and ankylosing spondylitis
Primary Dysmenorrhea
Postoperative pain and inflammation following cataract surgery
What is Arthrotec used for?
In patients with risk of gastric or duodenal ulcers
Diclofenac + Misoprostol
What are the ADRs of Diclofenac (and Arthrotec)?
GI symptoms
Modest ALT elevation
Dizziness, Headache
Arthrotec contraindicated in pregnancy
Metabolized by Cyp2C9
What is oral indomethacin and its uses?
Indoel derivative, slightly specific for COX1
Acute gouty arthritis
RA and osteoarthritis
Tendinitis
Ankylosing sponylitis
What is IV indomethacin used for?
Nonsurgical repair of patent ductus arteriosus
Decreases PGE levels
What are the ADRs of Indomethacin?
GI pain - take with food
Severe frontal headache
Displacement of bilirubin from albumin
Decreased urine output
What are the contraindications for indomethacin?
Hyperbilirubinemia
Renal failure
What is celecoxib?
Selective COX-2 inhibitor
What are the uses for celecoxib?
RA and Osteroarthritis
Ankylosing spondylitis
Primary dysmenorrhea
What are the drug interactions of celecoxib?
Metabolized by P450 Cyp2C9
Fluconazole
Inhibits 2D6
What are the ADRs of celecoxib?
GI pain
Nausea
What are the effects of NSAIDs during pregnancy?
Inhibit uterine motility
Induce bleeding in last trimester
Premature closing of ductus arteriosus
What are the functions of PGE2 in the kidney?
Increase GFR and renal blood flow
Inhibits Cl reabsorption in the TAL of LoH
Inhibits ADH on collecting tubules
Stimulate renin release
*NSAIDS reduce these effects
What are the effects of NSAIDs on the kidney?
Hyperkalemia and Water Retention
What is the MoA of acetominophen?
Weak inhibitor of COX-1/2
What are the therapeutic uses for acetominophen?
MIld to moderate pain
Preferred in children with viral fever
What are the ADRs of acetaminophen?
Hepatic toxicity (#1 drug cause)
Renal toxicity with chronic use
What are DMARDs?
Disease Modifying Anti-Rheumatic Drugs
Immune modulators believed to resotre normal immune environment within the joint synovium
Does not inhibit COX
