UWORLD Chapter 46: Systemic Steroids & Autoimmune Conditions

What can steroids be used for?

inflammatory conditions (psoriasis, acute asthma exacerbation), immunosuppression post transplant, and adrenal insufficiency.

What systemic steroids are commonly used as adrenal hormone replacement therapy? Why?

hydrocortisone, cortisone, and prednisolone

They have more glucocorticoid activity (anti-inflammatory effects)

What type of steroid is fludrocortisone and what is it used for?

mineralocorticoid activity (maintains water & electrolyte balance), used to treat Addison's disease and sometimes orthostatic hypotension

What can systemic steroids cause the adrenal gland to do?

stop producing cortisol through feedback inhibition, AKA suppression of the hypothalamic pituitary adrenal (HPA) axis

What is Cushing's syndrome?

excessive cortisol production by adrenal cortex or if exogenous (steroids taken at doses higher than normal

What is Addison's disease?

the adrenal gland doesn't make enough cortisol

What can Addison's disease lead to?

adrenal crisis (Addisonian crisis) which is characterized by volume depletion and hypotension, which can be fatal

What are physical features of Cushing's syndrome?

- Psychiatric changes: depression, impaired cognition

- Moon face

- Dorsocervical and supraclavicular fat pads

- Hirsuitism

- Muscle wasting, central obesity, striae

- HTN

- Osteoporosis

What are ways to reduce systemic risks of steroids?

- use every other day dosing

- For joint, use intra-articular injections

- For GI, use steroid with low systemic absorption

- For asthma, use inhaled steroids

- for transplants or severe autoimmune conditions, use lowest effective dose for the shortest amount of time.

What is the order of potency of steroids from least to most potent?

Cortisone

Hydrocortisone

Prednisone

Prednisolone

Methylprednisolone

Triamcinolone

Dexamethasone

Betamethasone

What are the short acting steroids and the equivilance factor strength used when converting to different steroids?

Cortisone 25mg

Hydrocortisone 20mg

What are the intermediate acting steroids and the equivilance factor strength used when converting to different steroids?

Prednisone 5 mg

Prednisolone 5 mg

Methylprednisolone 4 mg

Triamcinolone 4 mg

What are the long acting and highest potency steroids and the equivilance factor strength used when converting to different steroids?

Dexamethasone 0.75 mg

Betamethasone 0.6 mg

What is the helpful pneumonic to help remember steroid potency from least to greatest?

Cute - Cortisone

Helpful - Hydrocortisone

Pharmacists & - Prednisone

Physicians - Prednisolone

Marry - Methylprednisolone

Together & - Triamcinolone

Deliver - Dexamethasone

Babies - Betamethasone

What is an important administration counseling point for steroids

Take with food to avoid GI upset

What is the brand name of hydrocortisone?

Solu-Cortef

What is the brand names of methylprednisolone?

Medrol, Solu-Medrol

What is the brand name of prednisolone?

Millipred, Orapred ODT

What is the brand name of triamcinolone?

Kenalog

What is the safety warning for systemic steroids?

Adrenal suppression, if used for for than 14 days, taper dose slowly

What are short term side effects of steroids (< 1 month)?

Fluid retention, stomach upset, emotional instability, insomnia, increased appetite, weight gain, acute increase in BG & BP

What are long term side effects of steroids?

increased LDL and TG, cushing's syndrome

What is cortisone a prodrug of?

cortisol

What is prednisone a prodrug of?

prednisolone

Which steroid comes in a tapering dose pack for acute inflammation?

Methylprednisolone

What dosage/length of time of oral steroids is the definition of immunosuppression from steroids and therefore should be tapered slowly?

using 2 or more mg/kg/day or 20 mg or more per day of prednisone or a prednisone equivalent for > 2 weeks

What are common symptoms of most autoimmune diseases?

fatigue, weakness, pain

What are nonspecific laboratory blood tests that indicate inflammation?

erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and anti-nuclear antibody (ANA)

What can strong immunosuppressants increase the risk of?

- Reactivation of tuberculosis or hepatitis B or C: test and diagnose potential Hepatitis before steroids initiated

- Viruses: live vaccines given prior to steroids

- Lymphomas and certain skin cancers

- Infections

What is rheumatoid arthritis?

a chronic progressive disease causing inflammation in the joints and resulting in painful deformity and immobility, especially in the fingers, wrists, feet, and ankles.

What characteristics are consistent with a rheumatoid arthritis diagnosis?

- bilateral, symmetrical inflammation with pain

- Stiffness and pain worse at rest (morning stiffness)

What differentiates rheumatoid arthritis from osteoarthritis?

OA does not cause prolonged stiffness

What lab values are useful in diagnosing rheumatoid arthritis?

Anti-citrullinated peptide antibody (ACPA), and rheumatoid factor (RF)

What are classic joint symptoms of RA?

Swelling, pain, stiffness, bone deformity, weakness, difficulty moving, edema, redness

What should be started in all patients with symptomatic RA?

disease modifying anti rheumatic drug (DMARD), regardless of severity

What do DMARDs do?

slow the disease process and prevent further joint damage

What is preferred initial therapy for RA?

Methotrexate (MTX)

What can happen if 2 DMARDS are given at the same time?

risk of serious fatal infection, never combine two together

What is the use of steroids in RA?

RA flares at the lowest dose and for the shortest duration

What is the dosing of methotrexate in RA?

7.5-20mg once weekly (PO, SC, IM)

Why is methotrexate not dosed daily in RA?

liver damage

What's the MOA of MTX?

irreversibly binds and inhibits dihydrofolate reductase, inhibiting folate, thymidylate synthetase and purine

What are the two testable brand names and dosage forms of MTX?

- Oral: Trexall

- SC auto injectors: Otrexup and Rasuvio

What are the boxed warnings for MTX?

hepatotoxicity, myelosuppression, mucositis/stomatitis, pregnancy

What should be monitored while taking MTX?

CBC, LFTs, chest X-ray, hepatitis B and C serologies

Why should patients using MTX supplement folate?

to decrease hematological, GI and hepatic side effects

What is the brand names of hydroxychloroquine?

Plaquenil

What are safety warnings with hydroxychloroquine?

Irreversible retinopathy and QT prolongation

What are side effects and monitoring for hydroxychloroquine?

vision changes (dose related), eye exams at baseline and every 3 months

What is the contraindication of sulfasalazine?

Sulfa or salicylate allergy

What is the characteristic side effect of sulfasalazine?

can cause yellow-orange coloration of skin/urine

What is the MOA of leflunomide?

Inhibits pyrimidine synthesis

What are boxed warnings of leflunomide?

pregnancy (teratogenic) also a contraindication

hepatotoxicity: avoid in pre-existing liver disease or ALT >2x ULN

What are two counseling notes for leflunomide to remember for the NAPLEX?

- accelerated drug elimination options

- Use two forms of birth control during treatment, wait 2 years after discontinuation to conceive or use accelerated drug elimination procedure

What is the mechanism of tofacitinib, baricitinib, and upadacitinib?

inhibit janus kinase enzymes, which stimulate immune cell function

What are the boxed warnings of tofacitinib, baricitinib, and upadacitinib?

serious infections, malignancies, thrombosis

What should janus kinase inhibitors not be used with?

DMARDS or potent immunosuppressants

What are drug interactions with MTX?

• alcohol due to increased risk of liver toxicity,

• renal elimination decreased by aspirin and NSAIDS,

• Sulfonamides and topical tacrolimus increase side effects of MTX

• MTX can decrease effectiveness of loop diuretics and loop diuretics can increase MTX concentration

What is the mechanism and generic names of the anti-TNF inhibitors?

Tumor necrosis factor (TNF) alpha inhibitors

Etanercept, Adalimumab, Infliximab, Certolizumab pegol, Golimumab

What is the brand name of Etanercept, frequency of dosing, and does it need to coprescribed with methotrexate?

Enbrel

SC weekly

+/- MTX

What is the brand name of Adalimumab, frequency of dosing, and does it need to coprescribed with methotrexate?

Humira

SC every other week

+/- MTX

What is the brand name of Infliximab, frequency of dosing, and does it need to coprescribed with methotrexate?

Remicade

IV in normal saline at weeks 0, 2, and 6, then every 8 weeks

Coprescribed with MTX

What are the two types of reactions that occur with infliximab and the timing of each of them?

Infusion reaction: fever, chills, decrease BP (premedicate with acetaminophen, antihistamine, and steroids)

Delayed HSN reaction: 3-12 days after administration (fever, rash, HA, myalgia)

What is the brand name of Certolizumab pegol, frequency of dosing, and does it need to coprescribed with methotrexate?

Cimzia

SC at weeks 0, 2, and 4 then every other week thereafter

+/- MTX

What is the brand name of Golimumab, frequency of dosing, and does it need to coprescribed with methotrexate?

Simponi

SC monthly

Coprescribed with MTX

Which anti-TNF biologic requires a filter ?

infliximab and golimumab

What are the boxed warnings of anti-TNF biologics?

- serious infections including TB, fungal, viral, bacterial or opportunistic

- lymphomas and other malignancies

What are safety warnings of anti-TNF biologics?

can cause demyelinating disease, hepatitis B reactivation, HF, lupus like syndrome, hepatoxicity.

Don't use with other DMARDS or live vaccines

What should be monitored while taking Anti-TNF biologic DMARDS?

screen for TB and HBV prior to initiation, monitor for signs of infection routinely

What are storage notes with Anti-TNF biologic DMARDS?

dont shake or freeze, requires refrigeration

What do all biologic DMARDS have?

a pregnancy exposure registry

What is the MOA of rituximab (rituxan)?

Binds to CD20 on B cell leading to B cell depletion, given in combination with MTX

What are the premedications for rituximab?

steroid, acetaminophen, and antihistamine

What are the boxed warnings of rituximab?

serious and fatal infusion related reactions

HBV reactivation; screen high risk groups for HBV and HCV prior to using

Do not give with other biologic DMARDS or live vaccines

What is the MOA of anakinra?

IL-1 receptor antagonist

What is the safety warning of anakinra?

malignancies and serious infections

What is the MOA of Abatacept (Orencia)?

Inhibits T-cell activation by binding to CD-80 and CD-86 on antigen presenting cells (blocking interaction with CD28)

What are the DMARDS that are IL-6 receptor antagonists?

Tocilizumab and Sarilumab

What are the boxed warnings of the IL-6 receptor antagonists?

serious infections, screen for TB, dont give with other biologic DMARDS or live vaccines

Where can the MTX autoinjector be administered?

abdomen or upper thigh

What biologics can be stored at room temperature for 14 days?

etanercept and adalimumab

What are the admin sites of adalimumab?

abdomen and thigh

What are the admin sites for etanercept?

abdomen, thigh, or upper arm

Where are the admin sites of golimumab?

abdomen, thigh, and upper arm

Who is Systemic Lupus Erythematosus most commonly seen in?

females of African American or Asian decent

What are symptoms of Systemic Lupus Erythematosus?

flat red rash across the nose bridge and cheeks, often called a butterfly rash.

fatigue, depression, anorexia, weight loss, muscle pain, photosensitivity, joint pain, and stiffness

What manifestations of SLE contribute to the morbidity and mortality of this disease?

renal (including lupus nephritis), hematologic, and neurologic

What are common lab findings in patients with SLE?

Antinuclear antibodies (ANA)

Anti-single stranded DNA (anti-ssDNA)

Anti-double stranded DNA (anti-dsDNA)

Anti phospholipid antibodies

What are specific drugs that can cause drug induced lupus erythematosus (DILE)?

Methimazole, PTU, Methyldopa, Minocycline, Procainamide, Hydralazine, Anti-TNF drugs, Terbinafine, Isoniazid, Quinidine

What is a common side effect of SLE and how is that managed?

Photosensitivity, sunscreen and sun protection and avoidance are required

What do patients with mild SLE use for drug treatment?

hydroxychloroquine alone

What do patients with severe SLE use for drug treatment?

cyclophosphamide, azathioprine, mycophenolate mofetil, cyclosporine, or belimumab

How long does it take for some patients to see maximal treatment for SLE?

up to 6 months

What is the brand name and MOA of belimumab?

Benlysta

IgG1 lambda monoclonal antibody, reduces the activity of B cell mediated immunity

What is the MOA of anifrolumab?

human IgG1 kappa moAB against type 1 interferon receptors (dampens excessive type 1 interferon signature that is found in vast majority of adults and children)

What is the mechanism of calcineurin inhibitors?

suppresses immune system by inhibiting T lymphocyte activation

What are safety warnings with all monoclonal antibodies?

don't give with other DMARDS or with live vaccines

What are the boxed warnings of calcineurin inhibitors in SLE?

infections, malignancy

What are unique safety warnings of calcineurin inhibitors in SLE?

nephrotoxicity and hypertension, side effects include HTN, diarrhea, headache, and renal impairment

What is multiple sclerosis?

a chronic, typically progressive disease involving damage (demyelination) to the sheaths of nerve cells in the brain and spinal cord, whose symptoms may include numbness, impairment of speech and of muscular coordination, blurred vision, and severe fatigue.