Pharm Final - Drugs For Pain, Inflamation, And Arthritic Disorders

Front 1

define inflamation

Back 1

1) a normal protective response to tissue injury caused by physical trauma, noxious chemicals or micrologic agents
2) the body's effort to inactivate or destroy invading organisms, remove irritants ans set the stage for tissue repair

Front 2

What happens in inflamation?

Back 2

1) blood vessels dialate
2) increase vascular permeability
3) increased leukocyte accumulation

Front 3

mediators of inflamation

Back 3

1) histamine
2) kinins
3) neuropeptides
4) cytokines
5) eicosanoids (arachadonic acid metabolites)

Front 4

prostoglandins

Back 4

1) unsaturated FA derivitaves
2) produced in minute quantities in all tissues
3) act locally on tissue where they are produced
4) rapidly metabolize into their inactive metabolite at their site of action
5) Do NOT circulate in blood in significant quantities

Front 5

therapudic indications for NSAID's

Back 5

1) inflamation
--erythema, edema, hyperalgesia
***prostoglandins and other cell mediators
***autoimmunity (RA)
***infectious agents, ischemia, physical injury
2) Pain
--sensitization of pain fibers by prostoglandins
3) Fever
--pyrogenic stimulus release cytokines, increase prostoglandins in the hypothalmus, increase temp, and decrease heat loss

Front 6

Overview of NSAID's

Back 6

1) differing antipyretic, analgesic, and anti-inlamatory activity
2) inhibits COX but not lipoxygenase enzymes
3) COX 1 is constituitive
---platelets, kidneys, and GI tract
4) COX 2 is inducible and associated with inflamation
--less gastric damage caused by COX-2 than is with COX-1 inhibitors

Front 7

side effect of COX-1 inhibition

Back 7

inability to form stomach protecting prostoglandins

Front 8

Pharmicokinetics of aspirin

Back 8

1) AKA acetylsalicylic acid (ASA)
2) absorbed in the stomach and the duodenum
3) low gastric pH keeps most ASA in the non ionized form, which enhances absorption
4) rapid absorption leads to high concentration in gastric mucosal cells resulting in irritation of mucosal lining
5) buffering (gastric pH >3.5) can decrease irritationby slowing the absorption rate

Front 9

phase metabolism of aspirin

Back 9

hydrolyzed by esterase in the tissue and blood --> acetic acid + salicylate

Front 10

phase 2 metabolism of aspiin

Back 10

1) conjugated with glycine (liver)
--water soluble conjugate is excreted in the urine (kidneys)

Front 11

peak plasma level for aspirin occurs in ______(time)

Back 11

15 min

Front 12

peak plasma level for sallicylateoccurs in ______(time)

Back 12

1-2 hours

Front 13

serum half life of salocylates =

Back 13

low dose =3-5 hours
high doses = 15 hours

Front 14

MOA for aspirin and salicylate

Back 14

1) aspirin = irreversible COX inhibitor
2) Salycilate = reversible COX inhibitor
-----decreases prostoglandin synthesis

Front 15

effect of decreasing prostoglandin synthesis

Back 15

1) antiinflamatory
--PG mediates inflamatory events
2) analgesic
--PG thought to sensitize nerve endings to bradykinin, histimine, and other chemical mediators
3) Antipiuretic
--PG increases set-point in the hypothalmus periphreal vasodilation and sweating

Front 16

thromboxane is a product of

Back 16

COX-1

Front 17

fx of thromboxane

Back 17

increase platelet aggregation

Front 18

Prostoglandin is a product of

Back 18

COX-2 (from endothelial cells, and inflamatory cells)

Front 19

Fx of prostoglandins (dealing with platelet aggregation)

Back 19

decrease platelet aggregation

Front 20

aspirin at low doses_________

Back 20

<80 mg / day can irreversibly inhibit TXA2 production in platelets w/o affecting prostoglandin production in the endothelial cells

Front 21

adverse effect of aspirin and other salycilates

Back 21

1) GI
--epigastric destress, nausea, vomiting, and microscopic GI bleeding
2) blood
--prolonged bleeding time
--no ASA for 1 week prior to surgery
3) respiration
--toxic doses can cause respiratory depression, respiratory and metabolic acidosis
***warning sign = tinnitus

Front 22

Misoprostol

Back 22

PFE1 analog, reduces NSAID induced ulcers

Front 23

Tx for aspirin overdose

Back 23

1) Gastric lavage
2) I.V. sodiumbicarbonate
--alkalinize the urine promotes excretion (by trapping salycilates in the ionized form)

Front 24

Non selective COX inhibitors

Back 24

reversible
analgesic
anti-inflamatory
antipyretic

Front 25

examples of non selective COX inhibitors

Back 25

Ibprofen
indomethacin
ketoprofen
ketorolac
naproxen
piroxicam

Front 26

t1/2 of non selective COX inhibitors

Back 26

Ibprofen (2h)
indomethacin (5h)
ketoprofen (2h)
ketorolac (4-10h)
naproxen (14h)
piroxicam (57h)

Front 27

selective inhibitors for COX-2

Back 27

1) Celecoxib
2) rofecoxib (no longer on the market)
3) Valdecoxib (No longer on the market)

Front 28

Pharmicokinetics of Celoxib

Back 28

1) easily absorbed (peaks in 3 hours)
2) metabolized in the liver by cytochrome P450
3) excreted in feces and urine
4) once daily dosage (half life = 11 hours)

Front 29

Adverse effect of celecoxib

Back 29

1) abdominal pain, dyspepsia, and diarrhea
2) GI ulcers double that of the plecebo, but 1/3 of that taking IB profen, and 1/5 that of people taking neproxen
3) kidney toxicity
4) P450 interactions are likely

Front 30

acetaminophen

Back 30

1) tissue specific COX inhibitor
2) antipyretic and analgesic
--inhibits COX-3 in the CNS
3) NOT antiinflamatory
--minimal effect on COX in the periphery (inhibited by peroxides at the site of inflamation)
4) Metabolized in the liver
5) excreted in the urine

Front 31

Methotrexate

Back 31

immunosuppresant
--inhibits aminoimidazolecarboxamide (AICAR), transformylase, and thymidylate synthetase

Front 32

chlorambucil

Back 32

cross links DNA
--inhibits cell replication

Front 33

Cyclophosphamide

Back 33

cross links DNA
--inhibits cell replication

Front 34

cyclosporine

Back 34

Inhibits IL-1 and IL-2 receptor production
--dysrupts T cell mediated response

Front 35

TNF-alpha blocking agents

Back 35

1) adalimumab
2) Infliximab
3) Etanercept
4) Leflunomide

Front 36

function of adalimumab & Infliximab

Back 36

anti-TNF-alpha mAB
--inhibits macrophage and T cell function

Front 37

function of entanercept

Back 37

recombinant fusion protein
--TNF-alpha Rc IgG which binds to TNF alpha

Front 38

function of Leflunomide

Back 38

1) inhibits rhibonucleoside synthesis
--inhibits T cell proliferation

Front 39

define gout

Back 39

1)metabolic disorder with high serum levels of UA (deposited in the jonts and cartilidge)
2) many people have hyperuricemia w/o gout
3) urate crystals initiate inflamation

Front 40

risk factors for gout

Back 40

1) primary
--inherited abnormality in UA metabolism
2) secondary
--obesity
--high alcohol intake
--high BP
--abnormal kidney function
--drugs (thiazides and chronic low dose aspirin)

Front 41

DX of gout

Back 41

1) usually affects only 1 joint at a time
2) arthrocentesis - remove fluid from the joint and inspect for crystals
3) X-ray may shoe crystals deposits and bone damage

Front 42

Prophylactic tx of gout

Back 42

1) limit alcohol
2) drink pleanty of water
3) avoid foods rich in purines (shellfish, organ meats)
4) reduce weight

Front 43

drugs used to tx gout

Back 43

1) colchicine
2) probenecid
3) sulfinpyrazone
4)Allopurinol
5) NSAID's

Front 44

colchicine

Back 44

1) plant alkyloid
2) used for acute attacks of gout
--also prophylactically

Front 45

MOA of colchicine

Back 45

prevents polymerization of tubulin in microtubules
--inhibition of leukocyte migration into affected area
2) inhibits synthesis and release of leukotrienes

Front 46

MOA of Probenecid &Sulfinpyrazone

Back 46

1. Increases the excretion of uric acid by inhibiting the reabsorption of uric acid in the proximal tubule

Front 47

pharmicokinetics and metabolism of Probenecid & Sulfinpyrazone

Back 47

1. Completely absorbed in gut
2. peak plasma concentration 2-4 h
3. Half-life is dose-dependent (5-8 h)
4. 85-95% bound to plasma binding proteins

Front 48

MOA of Allopurinol

Back 48

Inhibitor of xanthine oxidase
---Purine analog (hypoxanthine isomer)



this reduces the production of uric acid

Front 49

allopurinol is metabolized to _________

Back 49

1) alloxanthine which retains capacity to inhibits XO
--this explains the the long duration of action

Front 50

__________NSAIDs are usually given first in acute gout attack

Back 50

1) non-salicylate NSAIDs
---Due to toxicity of colchicine,

Front 51

which NSAID's are most effec in tx gout

Back 51

b. Propionic acid derivatives most effective
--Ibuprofen
--Naproxen
--Ketoprofen

Front 52

can you use aspirin to tx gout?

Back 52

c. DO NOT USE ASPIRIN for gout
--It results in UA retention