Pharm II: Drugs for Bone & Joint Disorders

COX-1

expressed systematically and continuously; present in all tissues and cells

COX-2

inducible enzyme that is synthesized in response to pain and inflammation

Drugs used to treat osteoarthritis (OA)

NSAIDS

acetaminophen (Tylenol)

Misoprostol

COX-2 inhibitors

NSAIDs:

Acetylsalicylic acid (Aspirin)

Ibuprofen (Advil, Motrin)

Meloxicam

NSAIDs are more effective because they provide both _____ and _____ actions

analgesic and anti-inflammatory

for patients who have significant GI upset or adverse events, what medication should be prescribed with the NSAID?

H2 blocker

NSAIDs should not be used during

late pregnancy

NSAID usage should be stopped ______ before surgery

1 week

for a more rapid effect of NSAIDs, you can take NSAIDs

30 mins before food OR

2 hours after meals

______ while using NSAIDs may increase the risk of GI bleeding

alcohol

common NSAIDs

ibuprofen

naproxen

diclofenac

indomethacin

sulindac

meloxicam

ketorolac

etodolac

celecoxib

3 main clinical uses of NSAIDs

antipyretic

analgesic

anti-inflammatory

NSAIDs common adverse reactions

edema, rashes, tinnitus, GI bleed, peptic ulcers, renal failure, prolonged bleeding times, decreased hemoglobin, increased liver enzymes

salicylism

poisoning by NSAIDs and salicylates

Salicylism symptoms

tinnitus, hearing loss, mental disturbances, hyperventilation

severe NSAID intoxication symptoms

hyperthermia, dehydration

treatment of salicylism

sodium bicarb

all NSAIDs have drug interactions with:

anticoagulants, beta blockers, phenytoin, lithium, and loop diuretics

NSAIDs can increase

hypoglycemic effects of insulin

risk of bleeding with warfarin

when during pregnancy are NSAIDs contraindicated?

third trimester; may cause premature closure of ductus arteriosus

aspirin is often used in the treatment of ______ due to its anti-inflammatory effects

rheumatic diseases

(higher/lower) doses of aspirin are required for anti-inflammatory effect of aspirin, as compared to analgesic and antipyretic doses

higher

aspirin does/does not inhibit the formation of leukotrienes via the lipoxygenase pathway

does not

The acetylation effect of aspirin is (reversible/irreversible)?

irreversible

Because acetylation of the enzyme is irreversible, aspirins inhibitory effect on platelet aggregation lasts for up to

8 days

aspirin is absorbed mostly from the

upper small intestine

absorption from enteric coated preparations may be

erratic and slow

salicylate is highly bound to plasma proteins, primarily

albumin

at high and toxic doses, aspirin metabolism is _____ and occurs according to ______

limited, zero-order kinetics

at lower doses, aspirin metabolism proceeds according to

first-order kinetics

where is salicylate excreted?

in the urine

as the pH of the urine increases, _____ salicylate is excreted

more

Aspirin contraindications

hypersensitivity: pts with nasal polyps, asthma

children under 12 with a fever (Reye's syndrome)

Ibuprofen MOA

reversibly inhibits COX-1 and COX-2 -> decreased formation of prostaglandin precursors

ibuprofen chewable tablets contain ______, which is contraindicated in those who are sensitive to it

aspartame

which NSAID is the antirheumatic agent with the best tolerance?

Ibuprofen

Meloxicam adverse reactions

same as other NSAIDS, +

SJS, thrombocytopenia

Meloxicam may reduce the effects of

ACEIs, furosemide, & thiazide diuretics

Compared with other NSAIDs, meloxicam has significantly less

GI toxicity

what is the preferred drug for mild to moderate pain if there is no accompanying inflammation?

Acetaminophen (Tylenol)

how is acetaminophen dosed?

up to 1 gm, four times a day

acetaminophen adverse reactions

increased liver enzymes, hepatic failure, hepatotoxicity (overdose)

______ use with acetaminophen increases the risk of liver damage

barbiturates

do not take more than ____ of acetaminophen a day; can lead to hepatotoxicity

4 gm

adults should not take tylenol for more than _____ days and children for more than _____ days

10, 5

treatment for acetaminophen poisoning

N-acetylcysteine

N-acetylcysteine is effective if given less than _____ hours after ingestion of acetaminophen

24 hours

misoprostol MOA

synthetic prostaglandin E1 analogue with anti-secretory and mucosal protective properties

prevents gastric ulceration that NSAIDs are known to create

clinical use of misoprostol

patients with OA at high risk of developing ulcers

biggest adverse reaction of misoprostol

miscarriage

contraindication for misoprostol

pregnancy: increases uterine contractility

Cyclooxygenase-2 (COX-2) Inhibitors

celecoxib

celecoxib does not exhibit any _______ activity, which is an advantage over NSAIDs

antiplatelet

celecoxib clinical uses

RA

OA

dysmenorrhea

celecoxib adverse reactions

lower extremity edema, HTN, increased risk of MI and stroke, GI bleeding

celecoxib has higher risk of

renal toxicity

celecoxib black box warning

Cardiovascular and GI risks

do not use celecoxib in the setting of which type of surgery?

CABG

treatment for rheumatoid arthritis

Disease-modifying antirheumatic drugs (DMARDs)- slows progression of joint erosion

first line DMARD for RA

Methotrexate

Traditional DMARDs

methotrexate

Leflunomide

Hydroxychloroquine

What 3 situations can corticosteroids be used in treatment for RA?

1. early tx to provide symptomatic relief while waiting for a DMARD to work

2. in low doses chronically for patients who fail to get an adequate response from a DMARD

3. in bursts to treat acute flare-ups of disease

methotrexate MOA

folate antimetabolite that inhibits DNA synthesis, repair, and cellular replication

other clinical uses of methotrexate

psoriasis

SLE

sarcoidosis

antifolate chemotherapeutic drug

methotrexate adverse reactions

alopecia, photosensitivity, pruritus, N/A, mucosal ulceration, infertility, anemia, thrombocytopenia, increased liver enzymes, nephrotoxicity, osteonecrosis, stress fractures

Hematological toxicity of methotrexate increases when given with high doses of:

salicylates

NSAIDs

oral hypoglycemics

tetracyclines

sulfonamides

What herbals will interfere with the immunosuppression of methotrexate?

echinacea and melatonin

______ will lower the effect of methotrexate

caffeine

contraindications of methotrexate

pregnancy

chronic liver disease

in all patients taking chronic low dose methotrexate, it is recommended to prescribe _______ to reduce the risk of toxicities

folic acid or leucovorin (folinic acid)

Leflunomide MOA

Inhibits pyrimidine synthesis

leflunomide adverse reactions

alopecia, abnormal liver enzymes, back pain, bronchitis, dizziness

When a patient is taking leflunomide, you should watch for elevated

bilirubin & alk phos

Leflunomide contraindications

pregnancy

Hydroxychloroquine adverse reactions

QT prolongation, ototoxicity, visual disturbances, retinopathy

in a patient taking hydroxychloroquine, they require routine

eye exams

contraindications for hydroxychloroquine

preexisting retinopathy

gold compounds

Aurothioglucose

gold sodium

auranofin

gold compounds MOA are believed to interfere with

interleukin-1 (IL-1)

______ are used for suppression of synovitis during active stages of RA, but are not a cure.

IM gold salts

other clinical use of gold compounds

juvenile arthritis

common side effect of gold compounds

altered taste

contraindications for gold compounds

any hx of blood dyscrasias

dermatitis

colitis

patient education for gold compounds

watch for mouth ulcerations and skin rashes

Biologic DMARDs

TNF inhibitors

IL-6 inhibitors

JAK inhibitors

TNF inhibitors

Etanercept

Infliximab

Adalimumab

TNF inhibitors may be used concurrently with

methotrexate

TNF inhibitors adverse reactions

CHF, abd pain, neutropenia, UTIS, viral infections, URIs, bronchitis

TNF inhibitors black box warning

life-threatening infections (opportunistic infections), malignancy

TNF inhibitors contraindications

patients with serious infections

-TB

-sepsis

Before being put on a TNF inhibitors, patients must be tested/screened for

latent or active TB

IL-6 inhibitors

Tocilizumab- IV

Sarilumab- SubQ

clinical use of iL-6 inhibitors

patients with RA who are unresponsive to TNF inhibitors

JAK inhibitor

Tofacitinib- PO!!

what NSAIDs are preferred if being used for an acute gout attack?

naproxen or indomethacin

drugs used to treat Gout

allopurinol

colchicine

probenecid

sulfinpyrazone

Allopurinol belongs to a class called

xanthine oxidase inhibitors

Allopurinol has produced SJS when taken with

ACEis

You should warn patients of what when they first start taking allopurinol?

may see increased attacks of gout during initial treatment

Allopurinol enhances the anti-coagulation effects of

dicumarol