Pharm - Rheumatology

DMARDs

disease-modifying antirheumatic drugs

Methotrexate

conventional synthetic DMARD

inhibits dihydrofolate reductase to decrease DNA synthesis & lymphocyte proliferation & increase adenosine

Methotrexate indications

- RA (first line)

- juvenile idiopathic arthritis

- psoriasis

- polymyositis

Methotrexate BBWs

- hepatotoxicity

- bone marrow suppression

- pulmonary toxicity

- teratogenicity

- serious infection/malignancy

Methotrexate requires supplementation of what vitamin?

folic acid

Hydroxychloroquine (HCQ)

conventional synthetic DMARD

interferes with lysosomal activity & antigen presentation to decrease TLR signaling & cytokine release

HCQ indications

- RA combo therapy

- SLE

- Sjogren's

HCQ contraindications

preexisting retinopathy

HCQ requires what monitoring?

baseline & annual ophthalmology exam

HCQ adverse effects

- retinopathy (dose-related)

- GI upset

- skin hyperpigmentation

Leflunomide

conventional synthetic DMARD

inhibits dihydroorotate dehydrogenase to decrease pyridimine synthesis & decrease activated T cell proliferation

Leflunomide indications

- RA (alternative or add on to MTX)

- psoriatic arthritis

Leflunomide BBWs

- hepatotoxicity

- teratogenicity

Leflunomide monitoring

BP, LFTs, CBC

How can leflunomide be "washed out" for pregnancy or toxicity?

cholestyramine

Sulfasalazine

conventional synthetic DMARD

cleaved into sulfapyridine & 5-ASA to decrease prostaglandin & cytokine synthesis

Sulfasalazine contraindications

sulfa or salicylate allergy, GI or GU obstruction, porphyria

Sulfasalazine BBWs

- serious infections

- blood dyscrasias (aplasic anemia, agranulocytosis)

- SJS/TEN

Sulfasalazine adverse effects

- GI upset (take with food)

- reversible oligospermia

- yellow or orange urine/skin

Adalimumab

biologic DMARD (TNF inhibitor)

Adalimumab BBWs

increased risk of serious infections & malignancy

Adalimumab adverse effects

- injection site reaction

- demyelinating disease

- CHF exacerbation

- lupus-like syndrome

Adalimumab contraindications

- active serious infection

- demyelinating disease

- moderate to severe HF

Tocilizumab

biologic DMARD (IL-6 receptor antagonist)

Tocilizumab BBWs

increased risk of serious infections

Tocilizumab adverse effects

- neutropenia

- thrombocytopenia

- hyperlipidemia

- GI perforation

Tofacitinib

targeted synthetic DMARD (JAK inhibitor)

the only oral biologic!!

Tofacitinib BBWs

- serious infections

- malignancy

- major adverse cardiac events

- thrombosis

- mortality increase in older adults with CV risk factors

Abatacept

biologic DMARD (T cell costimulation modulator)

Abatacept has no

formal BBWs (but still risk of serious infections)

Abatacept adverse effects

COPD exacerbations

Rituximab

biologic DMARD (anti-CD20)

Rituximab BBWs

- fatal infusion-related reactions (within 24 hrs)

- Hep B virus reactivation

- progressive multifocal leukoencephalopathy (PML)

Rituximab requires premedication with

acetaminophen, antihistamine, & a corticosteroid

Prednisone

glucocorticoid

used as a bridge for DMARDs

Prednisone adverse effects

- HTN

- hyperglycemia

- osteoporosis

- weight gain

- mood changes

- infection risk

Prednisone patient education

- take with food in the AM

- do not stop suddenly

- take calcium/vitamin D supplements

Dexamethasone

corticosteroid

highest potency & long-acting

Hydrocortisone

corticosteroid

lowest potency

Ibuprofen

nonselective NSAID

inhibits COX1 & COX2 to decrease prostaglandin synthesis

Ibuprofen & Celecoxib BBWs

- serious GI bleeding

- serious cardiovascular thrombotic events (MI, stroke)

Celecoxib

COX2 selective NSAID

Celecoxib contraindications

- sulfa allergy

- hx of cardiovascular disease or stroke

What is the most GI-toxic NSAID?

Ketorolac (Toradol)

Which NSAID has the lowest CV risk?

Naproxen

Which NSAID is available in a topical formulation?

Diclofenac

Aspirin

nonselective, irreversible COX inhibitor

Aspirin adverse effects

- bleeding (no BBW)

- tinnitus

- renal dysfunction

Acetaminophen

non-NSAID analgesic

Acetaminophen dosing

max of 4g/day

Acetaminophen BBWs

- severe hepatotoxicity with overdose or >4g/day

- acute liver failure/death

A 48-year-old woman with RA is starting Methotrexate. Which of the following should also be prescribed routinely?

A. calcium carbonate

B. folic acid

C. vitamin B12

D. leucovorin rescue

E. iron sulfate

folic acid

Which of the following DMARDs is contraindicated in pregnancy & requires a cholestyramine washout if discontinuing for contraception?

A. HCQ

B. sulfasalazine

C. leflunomide

D. methotrexate

E. apremilast

leflunomide

A 35-year-old man with peptic ulcer disease & hypertension needs an anti-inflammatory for knee pain. Which is the safest option?

A. ibuprofen

B. naproxen

C. celecoxib

D. indomethacin

E. ketorolac

celecoxib

Colchicine

anti-inflammatory

used for acute gout flares & gout prevention during urate-lowering therapy

Colchicine adverse effects

- GI upset

- myopathy, rhabdo

- cytopenias

Colchicine dosing

dose limit of 1.8mg/day (risk of OD & organ failure)

Colchicine patient education

avoid grapefruit juice

Allopurinol

xanthine oxidase inhibitor

first line for chronic gout (urate lowering therapy)

Allopurinol BBWs

severe cutaneous adverse reactions (SJS, TEN, DRESS)

Febuxostat

xanthine oxidase inhibitor

indicated for chronic management of hyperuricemia in gout (allopurinol alternative)

Febuxostat BBWs

increased risk of cardiovascular death

Probenecid

Uricosuric agent

used adjunctively with allopurinol for chronic gout

Probenecid contraindications

- CrCl <50 mL/min

- hx of uric acid kidney stones

- high dose salicylates

Probenecid patient education

hydration is very important to prevent kidney stones (2+ L per day)

Lesinurad

selective uric acid reabsorption inhibitor (SURI)

used adjunctively with xanthine oxidase inhibitors (NOT monotherapy)

Lesinurad BBWs

acute renal failure when used as monotherapy

A 62-year-old man presents with a gout flare. He has a history of CKD (CrCl 35 mL/min). Which medication is least appropriate for treating his acute flare?

A. prednisone

B. colchicine

C. indomethacin

D. intra-articular steroid

E. low-dose naproxen

indomethacin (CI in renal impairment)

Which of the following must be emphasized for patients taking probenecid?

A. avoid high protein diets

B. maintain high fluid intake

C. avoid calcium supplements

D. avoid acetaminophen

E. take with milk

maintain high fluid intake

Duloxetine

SNRI

used in fibromyaglia for decreasing central pain perception

Duloxetine & Milnacipran BBWs

increased risk of suicidal thoughts & behavior in children

Milnacipran

SNRI

ONLY indicated for fibromyalgia

Pregabalin

anticonvulsant

used in fibromyalgia (decreases neuropathic & central pain signaling)

Pregabalin adverse effects

- euphoria

- dizziness

- blurred vision

- ataxia

Tramadol

atypical opioid analgesic

used for moderate pain when non-opioids are inadequate

Tramadol BBWs

- addiction

- life-threatening respiratory depression

- fatal sedation when used with other CNS depressants

- fatal toxicity when used with CYP2D6 metabolizers

Tramadol adverse effects

serotonin syndrome

Baclofen

GABA receptor agonist

Baclofen BBWs

abrupt discontinuation → fever, AMS, rebound spasticity, rhabo, organ failure

Baclofen adverse effects

weakness, sedation, hypotension

Tizanidine

Alpha 2 adrenergic agonist

used for muscle spasms and spasticity

Tizanidine adverse effects

sedation, dizziness, dry mouth, hypotension

Tizanidine patient education

do not stop abruptly (need taper to prevent rebound HTN)

Cyclobenzaprine adverse effects

sedation, anticholinergic effects, arrhythmias, QT prolongation

Morphine adverse effects

constipation, sedation, respiratory depression, tolerance

Which opioid has the highest potency?

fentanyl

Which opioid is safest?

buprenorphrine (partial agonist)

Which opioid is preferred in renal dysfunction?

hydromorphone (dilaudid)

What is the opioid antagonist?

Naloxone

A 45-year-old woman with fibromyalgia reports chronic fatigue, diffuse pain, & poor sleep. She has no depression or anxiety history. Which of the following is the most appropriate first-line option?

A. baclofen

B. tramadol

C. duloxetine

D. cyclobenzaprine

E. hydrocodone

duloxetine

Tramadol provides analgesia primarily through which dual mechanism?

A. COX2 inhibition & u-receptor agonism

B. weak u-receptor agonism & serotonin/norepinephrine reuptake inhibition

C. pure NMDA antagonism

D. dopamine reuptake inhibition and a2 activation

E. sodium channel blockade

weak u-receptor agonism & serotonin/norepinephrine reuptake inhibition

Which opioid is most appropriate in a patient with severe pain & renal impairment?

A. morphine

B. hydromorphone

C. codeine

D. tramadol

E. methadone

hydromorphone

Propofol adverse effects

- hypotension

- propofol infusion syndrome

- respiratory depression

Sevoflurane

inhaled anesthetic

Sevoflurane uses

induction & maintenance of general anesthesia (esp in pediatrics)

Rocuronium

Nondepolarizing neuromuscular blocker

competitive antagonist at ACh receptors

Rocuronium is always combined with

an anesthetic (only causes skeletal muscle paralysis)

Rocuronium reversal

cholinesterase inhibitors (Neostigmine or Sugammadex)

Succinylcholine

depolarizing neuromuscular blocker

does NOT have a reversal agent (must wear off naturally)

Malignant hyperthermia treatment

Dantrolene