Nsaids

Front 1

Arachidonic acid

Back 1

-released for cell membrane lipids by enzymes
-it is converted into many products by various enzymes (COX, lipoxygenases)
-COX 1 and COX 2 make prostaglandins and thromboxaneA2
COX 1 expressed all the time and assists with “housekeeping functions”
COX 2 is inducible by inflammation and immune cells

Front 2

Effects of PG and TXA2

Back 2

1. Vascular effects: PGs are vasodilators; TXA2 vasoconstrictor and inc smooth muscle mitogenesis
2. GI: protective effects, inc contractility, inc mucous secretion, inc blood flow, inhibit gastric acid secretion
3. Blood: TXA2 plt aggregator
4. Uterus: inc contractions
5. Kidney: inc RBF, provoke diuresis
6. Pain: PGs cause pain

Front 3

Misoprostol (PGE1)

Back 3

-used for GI protection and abortifacent (with mifepriston)

Front 4

Alprostadil

Back 4

-used for smooth muscle relaxing effects for ERECTILE dysfunction

Front 5

Latanoprost

Back 5

-topical agent for glaucoma

Front 6

Prostacyclin (PGI2)

Back 6

-synthesized by endothelial cells and vasodilator/anti-plt aggregator

(in contrast TXA2 cause vasoconstriction and plt aggregation_

Front 7

Dinoprostone

Back 7

-inserted into cervix
-used to induce labor

Front 8

other clinical effects of PGs

Back 8

-pulmonary HTN --> prostacyclin lowers pulmonary, coronary and peripheral resistance
-hypotension, HA, flushing
Iloprost
-patent ductus ateriosis: PGE1 is used to maintain an open PDA in neonates with certain congenital heart diseases before surgery

Front 9

intro to NSAIDS

Back 9

-aspirin is the prototype: irreversible covalent bond to COX so long lasting
-main MOA: inhibition of COX and therefore inhibition of prostaglandins

Front 10

therapeutic effects of NSAIDs

Back 10

-antipyretic, analgesic and antiinflamm
-reduce body temp in febrile states
-low to mod intensity pain relief including dental and postop pain
-chief clinical application as antiinflamm for muskuloskeletal pain, osteoarthritis, RA
-used to close a patent ductus arteriosus in neonate
-relief of menstrual cramps

Front 11

NSAIDs SE

Back 11

1. GI- most common in gastric upset. gastric or intestinal ulceration, bleeding
2. P - plt dysfunction
3. R- renal effects: dec RBF, promote Na and water retention which may reduce antiHTN meds
4. prolonged gestation and premature fetal PD closure (3rd trimester cat D)
5. hypersensitivity rxns: most common in pts with asthma, urticaria and nasal polys
-HYPERSENSITIVITY TO ASA IS A C/I TO USING ANY NSAIDS

Front 12

NSAIDs DI

Back 12

-may reduce effect of antihypertensives
-increases anticoagulant effects of warfarin

Front 13

The Salicylates

Back 13

1. Aspirin
2. Sulfasalazine
3. Olsalazine
4. salicylic acid (topical)
Uses: (of ASA)
1. antipyretics
2. analgesics
3. IBD
4. keratolytic action on warts
5. prophylaxis of CAD. DVT

Front 14

Aspirin

Back 14

-avail forms: enteric coated tabs, chewing gum, chewables, estended release tabs
-take with full glass of water or milk
-Cat D in preg

Front 15

Effects of Salicylates

Back 15

1. Respiration effects: stim CO2 production and stim respiration --? hyperventilation and resp alkalosis
2. Acid-base disturbances in salicylate intox also causes alterations of water and electrolyte balance
-toxic doses can lead to acidosis

Front 16

other effects of salicylates

Back 16

1. prolonged bleeding time/inhibits plt aggregation
2. antiinflamm/analgesic
3. antipytretic but do not use in kids due to risk of Reyes syndrome
4. Salicylism:High dosages can cause vomiting, tinnitus, vertigo and reversible hearing loss

Front 17

Diflunisal (Dolobid)

Back 17

-Rx tabs dosed every 8-12 hrs with meals
-rarely used

Front 18

Indomethacin (Indocin)

Back 18

-very potent
-main used for mod to severe arthritis, acute gouty arthritis
-toxicity:
1. frontal HA!
2. GI
3. CNS sx
4. renal ischemia and ARF
4. leukopenia, thrombocytopenia

Front 19

Sulindac (Clinoril)

Back 19

-less potent than indomethacin and used for osteoarthritis, RA, AS and acute shoulder bursitis, tendinitis
-non selective

Front 20

Etodolac (Lodine)

Back 20

-major difference is more COX2 selectivity so less GI toxicity than non selective NSAIDS
-OA, RA and postop pain
-AE:
1. CNS effects
2. asthenia
3. dizzy, drowsy
4. lower GI toxicity- dyspepsia, diarrhea, abd pain

Front 21

Ketorolac (toradol)

Back 21

-potent analgesic- moderate antiinflamm actions
-only parenteral NSAID
-IM or IV for postop or mod to severe acute pain for short term pain control and is used topically for seasonal allergic conjunctivitis and ocular inflammm
-higher incidence of GI toxicity and renal problems so use for short term only

Front 22

Diclofenac (Cataflam, Voltaren)

Back 22

-uses: long term RA, OA, AS
-also prepared with misoprostol as arthrotec to prevent GI erosion, ulceration
-potent antiinflamm effects
-AE:
1. GI
2. inc LFTs
3. CNS effects

Front 23

Ibuprofen (motrin, advil, nuprin)

Back 23

-Rx tabs, OTC oral drops, suspension, labs, liqui-gels
-uses: antipyretic, dysmenorrhea, MS pain, postop pain, arthritis, gout
-antiinflamm dosages higher than analgesic does
-AE:
1. GI-epigastric pain, nausea heart burn

Front 24

Fenoprofen

Back 24

-oral
-similar potency to ASA but better GI tolerability
-rarely used to cases of interstitial nephritis

Front 25

Ketoprofen

Back 25

-may have additional antiinflamm effects
-oral
-better tolerability than ASA
-watch for edema and creatinine increases esp in elderly

Front 26

Naproxen (Aleve, Naprosyn, anaprox)

Back 26

-OTC and Rx
-uses: dysmenorrhea, RA, OA, AS, JRA and acute gout
-potent COX inhibitors --> ASA and IBU
-dosed BID
-AE:
1. better tol than indomethacin
2. GI effects--> GI bleed
3. CNS effects
4. inc risk of CV effects?

Front 27

Nambumetone (relafen)

Back 27

-RA/OA
-converted to active metabolite that is potent COX inhibitor
-AE:
1. may have lower GI ulceration
2. rash, HA, pruritis
3. abd cramps, abd pain, diarrhea, dyspepsia, heartburn, indigestion

Front 28

Oxicams

Back 28

-Meloxicam
-OA, Ra
-oral
-COX 2 inhibition 10 fold to COX1
-less GI effects

Front 29

Coxibs

Back 29

-COX2 selective so less GI AE
-for OA, RA and acute pain
1. Celecoxib (celebrex)
2. Rofecoxib (Vioxx)
3. Valdecoxib (Bextra)

Front 30

Coxibs AE

Back 30

-inc CV risks and thrombotic events associted with COX 2 inhibitors
-Vioxx withdrawn
-Celecoxib is the only one currently on the market
-Celebrex: HA, CV and GI risks

Front 31

Disadvantages of COX 2 inhibitors

Back 31

-"Prothrombotic states"
-COX 1- makes TXA2 in plts, traditional NSAIDs and ASA block COX 1 and COX 2 so less thromboxane
-COX 2- makes prostacyclin so COX 2 selectively blocks prostacyclin production but thromboxane is still synthesized leading to imbalance and possible adverse thrombotic effects

Front 32

Anti-Gout drugs

Back 32

1. NSAIDs
2. Allopurinol
3. Uricosuric agents - increases rate of uric acid excretion
-Probenecib
-Sulfinpyrazone

Front 33

Colchicine

Back 33

-binds to tubulin and interferes with mitotic spindles and causes depolymerization and disappearance of the microtubules in granulocytes
-inhibits activity and migration of PMNS into inflammed area

Front 34

Colchicine pharm

Back 34

-rapid oral absorption
-diarrhea, N/V common early effects
-long term tx carries some risk of agranulocytosis and aplastic anemia
-myopathy and neuropathy can occur
-renal damage at toxic doses

Front 35

Colchicine effects a

Back 35

-for acute gout
-dramatic relief from acute relief of gouty attacks
-pain swelling and redness abate in 12 hrs and are gone in most pts by 48 hrs
-oral or IV
-may be used prophylactically when starting long term med to prevent acute attackes
-do not use in severe renal or hepatic dz
-start med ASAP

Front 36

Allopurinol (Xyloprim)

Back 36

-MOA: competitive inhibitor of xanthine oxidase which forms uric acid--> reduces uric acid concentration in the plasma
-prevents formation of uric acid kidney stones, dissolves tophi and prevents nephropathy
-oral
-excreted by kidney
-used in severe chronic gout

Front 37

Allopurinol toxicity

Back 37

1. hypersensitivity
2. initial increase in acute gout
3. maculopapular pruritic rash is most common- may be inc if give with amp/amoxicillin
4. caution in renal pts
5. DI --> enahnces uricosuric effect of probenicid
-also used for hyperuricemia due to chemo

Front 38

Uloric

Back 38

-chronic tx for gout
-xanthine oxidase inhibitor
-need to use with NSAID or colchicine to prevent flare of gout
-$$$
-AE:
1. liver function abnormlities
2. N
3. arthralgia
4. rash

Front 39

Corticosteroids

Back 39

-used for gout instead of NSAIDS esp in elderly
-short courses releives pain
-Prednisone or prednisolone for acute gout sx
-consider an intra-articular steroid injection if just a couple of joints are affected

Front 40

Pronenecid

Back 40

-MOA: uricosuric agent that blocks the reabsorption of uric acid in the proximal tubule
-chronic gout in underexcreters
-do not give in overproducers or pts with nephrolithiasis
-may prolong PCN effects by blocking renal excretion of PCN
-drink a lot of water to prevent uric acid stones
-cat B

Front 41

Probenecid AE

Back 41

1. mild skin rashes
2. HA
3. GI upset and aggrevation of PUD
4. may be used to block secretion of PCN and enhance effects of PCN
5. do not used in severe renal dysfunction
6. encourage liberal hydration
- Probenecid + Colchicine Tabs

Front 42

Sulfinpyrazone

Back 42

-MOA: competitive inhibitor of renal tubule reabsorption of uric acid
-AE:
1. upper GI distress
2. do not use in pts with hx of PUD
3. rash and hypersensitivity
4. svere blood dyscrasias