Chapter 46. Systemic Steroids and Autoimmune Conditions

Which drugs are more commonly used as adrenal replacement therapy and why?

• Hydrocortisone, cortisone, and prednisolone

• More glucocorticoid activity (anti-inflammatory) than fludrocortisone

What is fludrocortisone (mineralocorticoid activity to maintain water and electrolytes) used to treat?

Addison's Disease and orthostatic hypotension

Mimics Aldosterone

Why do steroids need to be tapered when they are discontinued?

Steroids may tell adrenal gland to stop producing cortisol (suppression of HPA)

Addison's Disease vs Cushing's

Addison's: Too little cortisol (volume depletion and hypotension can be fatal) -> Addisonian Crisis (adrenal)

Cushing's: Too much cortisol/steroids at high doses

Systemic Steroids (IV, PO) Dose Equivalents

Cute Helpful Pharmacists and Physicians Marry Together & Deliver Babies

25 mg Cortisone (s) -> prodrug of cortisol

20 mg Hydrocortisone (s)

5 mg Prednisone (i)

5 mg Prednisolone (i) -> prodrug of cortisone

4 mg Methylprednisolone (i)

4 mg Triamcinolone (i)

0.75 mg Dexamethasone (l)

0.6 mg Betamethasone (l)

Glucocorticoids and Brand names

• Dexamethasone (Decadron)

• Hydrocortisone (Solu-Cortef)

• Methylprednisolone ( Solu-Medrol, Medrol)

• Prednisone

• Prednisolone (Millipred, Orapred ODT)

• Triamcinolone (Kenalog)

Short-term side effects (Used <1 month) of Glucocorticoids

• Fluid rtn

• Stomach upset

• insomnia

• emotional instability

• increased appetite and weight gain

• Acute increase in glucose and BP

When is a patient considered immunosuppressed from steroids and should not receive live vaccines?

≥ 20 mg/day or ≥ 2 mg/kg/day for >2 weeks

Which medication is provided in a convenient taper kit with 21 x 4 mg tablets for a 6 day course?

Medrol therapy pack

What are nonspecific lab blood tests that can be useful in detecting inflammation?

ESR, CRP, RF, ANA

Risks of starting immunosuppressant treatment

• Reactivation of TB, Hep B, Hep C (testing and tx prior)

• Viruses - live vaccines should be given prior to tx

• Infections of various types

• Lymphomas and some skin cancers (suppressed by immune system normally)

Classic Articular Sx of RA

• Joint swelling

• Pain

• Stiffness (worse after rest; OA does NOT have prolonged stiffness

• Bone deformity

• Bilateral and symmetrical inflammation

What is the initial drug tx for ALL patients with symptomatic RA, regardless of severity, to slow the disease process?

DMARDs; Methotrexate preferred initially

*can add on other drugs, but never use a combination of biologic DMARDs

Which drug is used for RA flares?

steroids

MTX brand name

Trexall (oral tablet)

MTX MOA

Irreversibly binds and inhibits dihydrofolate reductase, inhibiting folate

Methotrexate Dosing for RA

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

*SC are auto-injectors (Otrexup, Rasuvo) in abdomen or upper thigh only

Boxed Warnings for MTX

Hepatotoxicity, myelosuppression, mucositis/stomatitis, pregnancy (teratogenic)

Monitoring: CBC, LFTs, Hepatitis B/C serologies, chest x-ray

What can be given with MTX to decrease hematological, GI, and hepatic side effects?

Folate (B9)

Hydroxychloroquine brand

Plaquenil

Warnings/Side effects of Plaquenil (Hydroxychloroquine)

• Vision changes (dose-related) -> monitor w eye exam

• Boxed Warnings: irreversible retinopathy, QT prolongation

Counseling for Sulfasalazine for RA

• Patients with sulfa or salicylate allergy

• Yellow-orange discoloration of skin/urine

Non-Biologic DMARDs for RA

• MTX

• Hydroxychloroquine

• Sulfasalazine

• Leflunomide

Leflunomide MOA

Inhibits pyrimidine synthesis (anti-proliferative)

Boxed Warnings for Leflunomide

• Teratogenic

- Requires negative pregnancy test prior and use 2 forms of birth control

• Hepatotoxicity

If one wants to become pregnant and received treatment for RA with leflunomide, how long must they wait?

• 2 years OR

• Accelerated drug elimination procedure:

1. Cholestyramine 8g PO TID x 11 days

2. Activated charcoal suspension 50g PO Q12H x 11 days

Boxed Warnings for JKIs

• Serious infections

• Malignancy

• Thrombosis

do NOT use w biologic DMARDs

MTX drug interactions

• Do not use with alcohol (liver tox risk)

• Renal elimination decreased by aspirin/NSAIDs

Anti-TNF Biologic DMARDs and Dosing

• Etanercept (Enbrel) -> SC weekly; abd, thigh, upper arm

• Adalimumab (Humira) -> SC QOW; abd or thigh

• Certolizumab pegol (Cimzia) -> SC QOW

• Infliximab (Remicade) -> IV in NS only

• Golimumab (Simponi) -> Monthly; abd, thigh, upper arm

EA CIG

Notes on all Anti-TNF Biologic DMARDs

• Each drug has a pregnancy registry

• Can be initial therapy (instead of MTX) in severe cases

• Do not shake or freeze - refrigerate

Which Anti-TNF Biologic DMARD is associated with infusion rxns and delayed hypersensitivity rxn?

Infliximab

Which anti-TNF biologic DMARDs MUST be used w/ MTX?

Infliximab and Golimumab (GI -> which is a BW of MTX!)

*Etanercept (Enbrel)/Adalimumab(humira)/Certolizumab(cimzia) can be used with or without

Which IV Anti-TNF DMARD must be used with a filter?

Golimumab

Boxed Warnings of Anti-TNF DMARDs

• Serious infections (screen for latent TB and tx if needed prior)

• Malignancies

Warnings for Anti-TNF Biologic DMARDs

• Demyelinating disease

• HB reactivation

• Hepatotoxicity

• Lupus-like syndrome

• Do not use w other biologic DMARDs or live vaccines

Rituximab (Rituxan) MOA for RA

Depletes CD20 B Cells

*non-TNF Biologic DMARD

T or F - Rituximab MUST be taken with MTX

True

Boxed Warnings for Anakinra (non-TNF biologic DMARD)

malignancies, serious infections (like all TNF-inhibitors)

Boxed Warnings for Rituximab

• infusion-related rxns

• HBV reactivation (screen high risk groups for Hep B/C)

Warning for Rituximab

Do not give with other biologic DMARDs or live vaccines

Boxed Warning for non-TNF Biologic DMARD, Tocilizumab?

Serious infections - screen for TB prior to therapy

Which biologic medications for RA can be stored at room temperature for a maximum of 14 days?

Adalimumab (Humira), Etanercept (Enbrel)

Select Drugs That Can Cause Drug-Induced Lupus Erythematosus (DILE)

My Pretty Malar Marking Probably Has a TransIent Quality

• MMI

• PTU

• Methyldopa

• Minocycline

• Procainamide

• Hydralazine

• Anti-TNF agents

• Terbinafine

• Isoniazid

• Quinidine

SLE is most common in which populations?

women of African American or Asian descent

Difference between SLE and DILE

DILE tends to stop after causative drug is discontinued

Clinical Presentation for SLE

• "Butterfly rash" (flat, red rash on nose and cheeks)

• Fatigue

• Depression

• Anorexia, weight loss

• Muscle pain, joint pain and stiffness

• Photosensitivity

Manifestations secondary to SLE

• Arthritis and cutaneous most common

• Renal, hematologic, and neurologic

• Lupus Nephritis (kidney disease) occurs in 50% of pts with SLE

Common laboratory findings in SLE

• Antinuclear antibodies (ANA)

• anti-ssDNA

• anti-dsDNA

Non Drug Tx for SLE

Sunscreen/protection and avoidance

Which drugs are treatment options for SLE?

• Hydroxychloroquine

• Cyclophosphamide

• Azathioprine

• Mycophenolate mofetil

• Cyclosporine

Up to x 6 months

Belimumab brand name

Benlysta (for Lupus/lupus nephritis)

*do not give with biologic DMARDs or live vaccines

*warning for infections

Warnings/Side effects associated with Voclosporin for lupus nephritis

• Boxed Warning: infections, malignancies

• Nephrotoxicity/renal impairment

• Hypertension

• Diarrhea

• Headache

MS is a chronic and progressive disease that attacks what?

Myelin sheath

Symptoms (early vs late) of MS

Early:

• numbness

• blurred vision

• fatigue

Late:

• cognitive decline

• muscle spasms

• pain

• bladder spasticity

• gait instability

What imaging can be used to help diagnose MS?

MRI for brain lesions

What drugs are used to treat MS?

• Interferon beta formulations ->IM weekly (Avonex) or SC 3x week (Rebif) for 1a; SC QOD (betaseron, extavia) for 1b

• Glatiramer Acetate (Copaxone) ->SC daily or SC 3x/week

• Pegylated interferon (Plegridy) -> Q2Weeks

What is the preferred treatment for MS in pregnancy?

Glatiramer acetate (Copaxone)

Warnings/Side effect of Glatiramer Acetate (Copaxone)

• Chest pain, flushing

• Injection site rxns

• Diaphoresis

• Dypsnea

Warnings/Side effects for Interferon beta products

• Psychiatric disorders

• Injection site necrosis

• Flu-like sx

• increased LFTs

• Thyroid dysfxn (hypo and hyper)

Counseling for interferon beta products

• Let come to room temp if refrigerated

• Do NOT expel air bubble in prefilled syringes d/t loss of dose

• Some formulations contain albumin - increased risks of Creutzfeldt-Jakob disease

Which testing is required prior to using the sphingosine 1-phosphate (s1p) receptor modulator Simponimod?

CYP2C93/3 genotype

What is the initial preferred treatment for relapsing remitting MS?

Oral DMTs (i.e. fingolimod)

Warnings/Side effects of S1P receptor modulators?

• Can cause bradycardia

• Fingolimod must be monitored for at least 6 hours after 1st dose with ECG

• Infection risk (monitor CBC), screen for VZV

• Macular edema (monitor w eye exams)

• Monitor LFTs

• MS can be become worse if tx is stopped

• Ozanimod: do not use w MAO inhibitor

Fumarates/Nuclear factor capsule counseling

DO NOT crush, chew, or sprinkle caps on food

Teriflunomide is a pyrimidine synthesis inhibitor that is contraindicated when?

In pregnancy

Which monoclonal antibody for MS has a Boxed Warning for a REMS program?

Alemtuzumab

Natalizumab (Tysabri) is a mAb for MS that is also used to treat what?

Chron's Disease

Natalizumab (Tysabri) Boxed Warning

PML; Only available through the REMS TOUCH program

What drug for MS can help to control tremor?

Propranolol

What drugs are used for sx control in MS?

• Anticholinergics for incontinence

• Laxatives for constipation

• Muscle relaxants for spasms/spasticity

• Analgesics for pain/spasms

• Propranolol for tremor

What triggers Raynaud's?

cold and/or stress -> leads to vasospasm in fingers/toes; skin turns white to blue

Which drug is most commonly used for Raynaud's?

Nifedipine (DHP CCB)

Drugs that cause/worsen Raynaud's

BBs

Bleomycin, cisplatin

Sympathomimetics (vasoconstriction): amphetamines, pseudoephedrine, and illicit drugs (i.e. cocaine and meth)

Celiac disease

immune response to eating gluten; protein found in wheat, barley, and rye

What is the primary and most effective tx for celiac disease?

AVOID gluten entirely

Present as a drug excipient

Common sx of celiac disease

diarrhea, abdominal pain, bloating, and weight loss

What key word should be looked for on medications in order to avoid gluten in excipients?

"starch" in ingredient list - may be corn, potato, tapioca, or wheat; contact MFR if not explicitly listed

Common symptoms of Myasthenia Gravis

• Eye/vision changes

• Drooping eyelid (Ptosis)

• Drugs can worsen/unmask MG

What class of drugs is used to treat myasthenia gravis

Cholinesterase inhibitors: Block breakdown of acetylcholine (i.e. Pyridostigmine)

*Cholinergic effects: SLUDD

Sjogren's Syndrome presentation

• dry eyes and dry mouth

• Commonly secondary to another autoimmune disease

• Complications: dental caries, corneal ulceration, and chronic oral infections

Treatment for dry eyes in Sjogren's syndrome?

• OTC artificial teardrops

• Cyclosporine eye drops (Restasis) -> counsel pts to use properly to avoid infection; ocular burning side effect

What medication for dry eyes has a unique side effect of unusual taste?

Lifitegrast (Xiidra) eye drops for Sjogren's syndrome

Treatment for dry mouth in Sjorgren's syndrome

• sugar-free gum (with xylitol)

• lozenges

• Daily rinses w antimicrobial mouth wash

• Rx muscarinic antagonists (i.e. pilocarpine, cevimeline)

When are muscarinic antagonists (i.e. pilocarpine, cevimeline) contraindicated?

Uncontrolled asthma and narrow-angle glaucoma

What are non-drug treatment options for psoriasis treatment?

UVB phototherapy (Causes activated t cells in skin to die, reducing proliferation) for mild to moderate sx

Topical options for treating psoriasis

• Steroids

• Vitamin D analog (calcipotriene)

• anthralin

• retinoids (some used for acne; tazarotene)

• salicylic acid (shampoo)

• coal tar

• tapinarof

• moisturizers

if failure: topical calcineurin inhibitors (i.e. Protopic, Elidel); preferred for face

Which drugs for psoriasis are also used for dandruff and dermatitis?

Coal tar; messy

What drug is only used for severe cases of psoriasis?

acitretin (oral)

Which drug for psoriasis can cause weight loss and diarrhea?

Apremilast; PDE-4 inhibitor

Which drugs for psoriasis are available as SC injection?

Interleukin receptor antagonists (mAbs) -> can cause serious infections, screen for TB ; diarrhea