Pharm Rheumatology and Autoimmune (Musculoskeletal Disorders)

Topical Agents for Osteoarthritis examples

Topical Diclofenac

Topical Capsaicin

preferred over systemic therapy

When are topical agents recommended vs not recommended for osteoarthritis

recommended for knee and conditionally for hand

not recommended for hip

topical diclofenac clinical pearls

this is an NSAID that carries the same warnings and contraindications as oral NSAIDS

contraindicated in non-intact or damaged skin

topical capsaicin mechanism of action

prevents re-accumulation of substance P, a chemomediator responsible for pain transmission from the periphery to the central nervous system (CNS).

topical capsaicin clinical pearls

comes from chili peppers

can cause burning and irritation (not recommended for hand d/t risk for eye contamination)

maximal effect after 2-4 weeks

contraindicated on non-intact skin

NSAIDS for OA examples

non-selective: diclofenac, ibuprofen

COX-2 selective: celecoxib

NSAIDS for OA clinical pearls

second-line therapy

BBW: inc risk for serious CV thrombotic events and GI events

can cause fluid retention and renal impairment (do not use with ACEI and ARBs)

risk for lithium toxicity d/t inhibition of lithium excretion

analgesics used for OA examples

duloxetine (Cymbalta)

Tramadol (Ultram)

Acetaminophen (Tylenol)

nonacetylated salicylates

only decrease pain and have no effect on inflammation

used in pts with contraindications to NSAIDS or OA in multiple joints

Duloxetine (Cymbalta) mechanism of action

SNRI: inhibits reuptake of serotonin and norepinephrine (this reduces pain transmission to the CNS)

Duloxetine contraindications

do not use within 14 days of MAOIs d/t risk for serotonin syndrome

duloxetine adverse effects

BBW: inc suicidal ideation in pts younger than age 25

hepatotoxicity, orthostatic hypotension, excessive sweating, constipation, somnolence, abnormal bleeding

Tramadol mechanism of action

Mu opioid receptor agonist: reduces pain sensation (similar to morphine)

inhibits reuptake of serotonin and norepinephrine

tramadol contraindications

opioid dependency

seizure hx

renal and hepatic dosing

do not use with SSRIs, TCAs, MAOIs, and linezolid d/t risk for serotonin syndrome

tramadol adverse effects

risk for addiction, abuse, misuse

lowers seizure threshold

life-threatening respiratory depression and CNS depression

euphoria

why is tylenol only conditionally recommended in OA?

questionable efficacy and risk for hepatotoxicity over time

nonacetylated salicylates for OA examples and mechanism of action

Diflunisal (Dolobid), sodium salicylate, choline salicylate, magnesium salicylate, choline magnesium trisalicylate (CMT, Tricosal), salsalate (Disalcid)

•May be beneficial in patients with sensitivity to GI irritation from long-term aspirin use

•Mechanism of Action: COX-1 inhibition -> mild anti-inflammatory and analgesic effects

intra-articular (into joint) corticosteroids for OA clinical pearls

as needed therapy

may be helpful if joints have not responded to first or second line therapy

generally recommended against d/t limited benefit and potential risk for harm

drugs that may worsen gout

thiazide and loop diuretics

cyclosporine

aspirin

Xanthin Oxidase Inhibitors (XOIs) for chronic gout examples

allopurinol (aloprim)

febuxostat (Uloric)

XOIs mechanism of action

decrease uric acid production

XOIs adverse events

allopurinol: rare life-threatening risk of hypersensitivity reactions (SJS, TEN) 

-recommended to do genetic testing for HLA allele to check for high risk for SJS

-impaired liver and kidney function

-leukocytosis and eosinophilia

febuxostat: BBW for inc risk of CV death

-reserved for pts not controlled on max dose of allopurinol

allopurinol interactions

ACEIs and loop diuretics may inc allopurinol levels

allopurinol may dec metabolism of warfarin, leading to inc bleeding risk

uricosuric agents for chronic gout example

probenecid (Benemid)

used if one XOI is contraindicated or not tolerated

probenecid mechanism of action

increases the excretion of serum uric acid

probenecid contraindications

not for acute gout attack (can exacerbate symptoms)

*Do not use with citalopram: risk for QT prolongation

blood dyscrasias, uric acid kidney stones

children less than 2

probenecid adverse events

hemolytic and aplastic anemia in pts with G6PD deficiency

hepatic necrosis

anyphylaxis

recombinant uricase example

pegloticase (Krystexxa)

injection that is last line for chronic gout, used if XOI or probenecid not successful

pegloticase mechanism of action

converts uric acid into metabolite that can be excreted by the kidneys

NSAIDS used for acute gout attacks

naproxen, indomethacin (Indocin), sulindac (Clinoril)

use of NSAIDS in acute gout

reduces pain and inflammation

initiate at the onset of gout and continue for 24 hours after resolution of symptoms

usual course is 3-7 days, relief in hours

corticosteroids for acute gout examples

prednisone, methylprednisolone

triamcinolone acetonide

use of corticosteroids in acute gout

reduces inflammation

5-10 day taper, relief in 1-2 day, up to 1 week for complete resolution

colchicine (Colcrys) mechanism of action

•inhibits the activation, degranulation, and migration of neutrophils to the area of a gout attack. This then decreases the inflammation and pain associated with a gout attack.

colchicine contraindications

renal/hepatic impairment

colchicine adverse events

diarrhea

pharyngolaryngeal pain

fatigue, headache

blood dyscrasias (may be a reason to d/c)

neuromuscular toxicity/rhabdomyolysis

colchicine use for acute gout

should be taken within 24 hours of symptom onset

can also be used as prophylaxis

drugs that may worsen osteoporosis

anticonvulsants

thyroid hormones

Depo-provera

lithium

GnRH agonists (ex: leuprolide)

PPIs

steroids

drug classes for osteoporosis tx

•Supplements (prevention): Calcium, vitamin D

•Bisphosphonates

•Calcitonin

•Selective estrogen receptor modulator

•Parathyroid Hormone (PTH) and Parathyroid Hormone-Related Protein (PTHrP) Analog

•Sclerostin Inhibitor

•RANK Ligand Inhibitor

bisphosphates examples

alendronate (Fosamax)

risedronate (Actonel)

Ibandronate (Boniva)

bisphosphates mechanism of action

inhibit bone resorption to increase bone density

administration of bisphosphates

poorly absorbed orally, must be taken on empty stomach in the morning

take with at least 8 oz of water and remain upright for at least 30 minutes to minimize reflux

separate supplements or antacids

bisphosphates contraindications

renal impairment

esophageal abnormalities

hypocalcemia

bisphosphates adverse events

GI issues

hypocalcemia and hypophosphatemia

musculoskeletal pain

esophageal issues

osteonecrosis and atypical femur fractures with long term use (although these meds may plug in the holes of bones, it may not be great quality bone)

calcitonin example and use

salmon calcitonin (Miacalcin)

used to treat osteoporosis in post menopausal women

calcitonin mechanism of action

directly inhibits osteoclast bone resorption

lowers blood calcium levels by slowing down bone breakdown

can be an injection or nasal spray

calcitonin adverse events

hypocalcemia

myalgia

hypersensitivity reactions

inc risk for malignancy (cancer) with long term use

Selective Estrogen Receptor Modulators (SERM) examples

raloxifene (Evista)

conjugated estrogens/bazedoxifene (Duavee)

raloxifene indication

treats and prevents osteoporosis

reduces risk of breast cancer in postmenopausal women with osteoporosis shown to reduce risk of vertebral fractures, no effect on hip fractures

conjugated estrogens/bazedoxifene (Duavee) indication

combination product used for prevention of osteoporosis in women with a uterus

shown to inc bone mineral density in lumbar spine and hip

SERMs mechanism of action

mimic the effects of estrogens on bones, without affecting the breasts and uterus

decreases bone resorption and bone turnover

SERM contraindications

Both meds:

pregnancy/breastfeeding

women with a hx of thromboembolic events

•Conjugated estrogens/bazedoxifene:

contraindicated in women with endometrial and breast cancer, in patients with dementia (not recommended for patients >75 years of age), and patients using additional estrogens

SERMs adverse events

•Raloxifene:

hot flashes

peripheral edema

flu-like symptoms

leg cramps, DVT

arthralgias

•Conjugated estrogens/bazedoxifene:

nausea, diarrhea, abdominal pain, dyspepsia

muscle spasms

parathyroid hormone and parathyroid hormone-related protein analog examples

Teriparatide (Forteo): PTH analog

Abaloparatide (Tymlos): PTHrP analog

parathyroid hormone and parathyroid hormone-related protein analog indication

indicated to treat postmenopausal women and men at high risk of fractures who have failed other therapies

also indicated in glucocorticoid-induced osteoporosis

role of PTH

regulates calcium, phosphate, and bone metabolism

stimulates new bone formation

teriparatide (forteo) mechanism of action

PTH analog that stimulates bone formation (osteoanabolic)

SQ injection

teriparatide and abaloparatide contraindications

Paget’s disease, previous bone radiation therapy, metabolic bone disease, hx bone cancer

children

hypercalcemia, hyperparathyroidism

caution in hx of kidney stones

2 year use limit d/t osteosarcoma risk

teriparatide and abaloparatide adverse events

leg cramps, arthralgia

orthostatic hypotension

hyperuricemia

hypercalcemia (lower risk with abaloparatide)

-may inc risk for dig toxicity

-may worsen kidney stones

RANK ligand inhibitor example and clinical pearls

Denosumab (prolia)

must be administered by healthcare provider

BBW for hypocalcemia in pts with CKD

prevents bone resorbption

Drug classes for Rheumatoid arthritis

• NSAIDS 

• Corticosteroids 

• DMARDS: most efficient, but until these provide relief, corticosteroids and NSAIDS can bridge the gap 

Disease-Modifying Antirheumatic Drugs (DMARDs) examples

Conventional synthetic DMARDs – Preferred DMARDs

Methotrexate (Rheumatrex)

Sulfasalazine (Azulfidine)

Hydroxychloroquine (Plaquenil)

Leflunomide (Arava)

DMARD therapy should be initiated within 3 months after onset of symptoms, if not immediately after diagnosis

Methotrexate mechanism of action

folic acid antagonist

•Inhibits production of mediators in signaling pathways, causing anti-inflammatory and immunosuppressive effects (leukocyte suppression)

half-life is short, but it is retained in the cells, so effects may last for days

MTX contraindications

pregnancy/breastfeeding

leukopenia and other blood dyscrasias

liver disease

infections (causes immunosuppression)

many drug interactions (ex: aspirin can inc MTX concentration)

MTX BBWs

risk of fetal death/severe abnormalities

*hepatotoxicity

renal impairment

pneumonitis

bone marrow suppression

diarrhea/ulcerative stomatitis

SJS/TEN

infections

malignancies

Sulfasalazine mechanism of action

•decreases inflammatory cytokine production, inhibits prostaglandin production, and blocks cyclooxygenase to produce anti-inflammatory effects

sulfasalazine contraindications

sulfonamide or salicylate allergy

GI or GU obstruction

porphyria (disease where hemoglobin is abnormally metabolized)

sulfasalazine adverse events

agranulocytosis

hepatotoxicity, nephrotoxicity

reversible sterility in men

hydroxychloroquine (Plaquenil) mechanism of action

Antimalarial drug, but for RA it causes anti-inflammatory effects 

hydroxychloroquine (Plaquenil) contraindications

retinal field changes (can cause retinal damage)

hydroxychloroquine (Plaquenil) adverse events

photosensitivity

skin pigmentation changes

retinal damage

QT prolongation

leflunomide (Arava) mechanism of action

inhibits folic acid synthesis and reduces inflammation

leflunomide contraindications

BBW for hepatotoxicity, do not use in hx of alcoholism or preexisting liver disease

pregnancy (2-year washout period for women, chlorestyramine can reduce half-life)

-has a very long half-life

leflunomide adverse events

bone marrow suppression

alopecia

elevated LFTs

may inhibit warfarin metabolism

Which DMARD falls into the JAK inhibitor class?

Tofacitinib (Xeljanz)

biologic disease: modifying antirheumatic drugs

tumor necrosis factor inhibitors

Etanercept (Enbrel)

infliximab (Remicade)

adalimumab (Humira)

golimumab (Simponi)

certolizumab pegol (Cimzia)

TNF inhibitors mechanism of action

prevents interaction of TNF-alpha on immune cell receptors -> blocks inflammatory cascade AND (2) trigger cell lysis upon binding to surface TNF-alpha

TNF inhibitors contraindications

infections, live vaccines

untreated hep B

CHF

solid malignancy within the last 5 years

TNF inhibitors adverse effects

injection-site and infusion rxn

infections

demyelinating CNS diseases

biologic disease: modifying antirheumatic drugs (non TNF inhibitor) example

Abatacept (orencia)

Tocilizumab (Actemra)

Sarilumab (Kevzara)

Rituximab (Rituxan)

Abatacept mechanism of action

blocks activation on T cells

Abatacept contraindications

•Hypersensitivity

•Caution in patients with history of infection – Screen for latent TB and hepatitis prior to initiation due to risk of reactivation

•Caution in history of COPD

•Live vaccine while on abatacept or for 3 months afterward

•Use of other DMARDs due to risk of immunosuppression

Abatacept adverse events

•Increased rate of COPD exacerbations, cough, pneumonia, dyspnea

•Common: Headache, hypertension, infusion-related reactions

•Anaphylaxis (rare)