NAPLEX Systemic Steroids & Autoimmune Conditions

Two primary endogenous steroids that can require replacement include:

What is the drug for each?

Cortisol: Replaced by giving steroids (glucocorticoid activity)

Aldosterone: Replaced by giving fludrocortisone

(Mineralocorticoid activity)

Fludroscortisone is FDA-approved for _______________

Often used off-label for _________________

It mimics what endogenous steroid

Addison's Disease

Off label: Orthostatic hypotension

Aldosterone

Glucocorticoids have more _________ activity

anti-inflammatory

(Compared to mineralocorticoid activity pertaining to water/Na balance)

What is the main risk of steroid use

HPA axis suppression - adrenal gland stops producing cortisol due to feedback inhibition

HPA = Hypothalamic-pituitary-adrenal

Cushing's syndrome is caused by

caused by prolonged exposure to high levels of cortisol (via adrenal malfunction or exogenous supply - drugs)

Signs of Cushing's syndrome

Central obesity (w thin arms/legs)

Glaucoma/cataracts

Acne

Fat deposit in face (moon face)/back (buffalo hump)

Pink/purple stretch marks, easily bruises

Impaired wound healing

GI bleed/esophageal tears

Women: Facial/body hair, Irregular/absent menses

Ways to decrease systemic steroid risk (2)

Alternate day dosing

For a condition in the gut, use steroid that with low systemic absorption (budesonide)

Steroids: Acronym for least to most potent (same order for short acting to longest acting)

Cute Hot Pharmacists and Physicians Marry Together and Deliver Babies

Cortisone (25mg)

Hydrocortisone (20mg)

Prednisone (5mg)

Prednisolone (5mg)

Methylprednisolone (4mg)

Triamcinolone (4mg)

Dexamethasome (0.75mg)

Betamethasone (0.6mg)

Systemic steroids: Dexamethasone

Brand?

DexPak 6, 10, or 13 day

Decadron

Systemic steroids: Hydrocortisone

Brand?

Solu-Cortef

Systemic steroids: Methylprednisolone

Brand?

Medrol

Solu-Medrol

Systemic steroids: Prednisone

Brand?

Deltasone

Systemic steroids: Prednisolone

Brand?

Millipred

Orapred ODT

Systemic steroids: Triamcinolone

Brand?

Kenalog

Counseling point for oral steroids

Take with food to decrease stomach upset

Must taper steroids slowly if taking

> ____ mg for > _____ days

> 20mg/d prednisone equivalent

for > 14 days

Short-term AEs of steroids

Increase appetite/weight gain

Increase blood glucose

Insomnia/sleep disturbance

Emotional instability

Steroids: ________ is a prodrug of cortisol

Cortisone

Steroids: Prednisone is a prodrug of ___________

Prednisolone

Common way to taper steroids

reduce dose by 10-20% every few days

Tapers can last 7-14 days (or longer/shorter depending on duration of use)

Common non-specific sx of autoimmune disease (3)

Fatigue

Weakness

Pain

Non-specific lab test that may be useful in detecting inflammation in those with possible autoimmune disease (4)

ESR

CRP

RF (Rheumatoid factor)

ANA (Anti-nuclear antibiody)

The utilization of strong immunosuppressants (for autoimmune diseases) can increase the risk of (3)

- Re-activation of Tuberculosis, Hep B/C (testing and Tx is needed before starting immunotherapies)

- Lymphomas and certain skin cancers

- Infection

Vaccination in those considering initiation of strong immunosuppressive therapies

LIVE vaccines much be given before starting immunotherapy

Recap: Things to consider giving your patient before starting strong immune therapies

Any LIVE vaccines that are indicated

Testing for Tuberculosis. Hep B and C - Tx if needed prior

Medrol therapy packs

-dosed over 6 days

-includes 21, 4 mg tablets

-start high, taper down

(Tabs spaced through day surrounding meals/bedtime)

Rheumatoid arthritis presentation

Bilateral, symmetrical disease of the joints (Joint swelling, Pain, Stiffness, Deformity)

Stiffness/pain are worse after rest

OA vs RA: morning stiffness

RA

OA vs RA: prolonged stiffness

RA

(OA does not cause prolonged stiffness)

What are 2 laboratory test that can he useful in diagnosing RA

Anti-citrullinated peptide antibody (ACPA)

Rheumatoid Factor (RF)

Patients with symptomatic RA should be initiated on ______

DMARD, regardless of severity

Role in therapy of DMARDs (goal)

Prevent further joint damage

Slow the progression of the disease

Treatment goal is remission/low disease activity

Which DMARD is first line for treatment of RA

Methotrexate (for most patients)

With or without a systemic steroid

For patients with more mod-severe RA, what is the treatment recommendation if methotrexate alone is not enough?

- Combination of DMARDs

- Tumor necrosis factor (TNF) inhibitor biologic

- Non-TNF biologic (+/- MTX)

Never use what combination of medication types to treat RA?

Never use 2 biologic DMARDs in combination

(Risk of fatal infections)

Low dose steroids are considered <_____mg /d

Place in treatment of RA?

< 10 mg pred eq /day

Can be added in patients with mod/high disease activity when starting DMARD therapy (bridge)

Can be used in patients who have failed DMARD

Used for RA flares (lowest dose/duration)

Non-biologic DMARDs for RA (6)

Methotrexate

Hydroxychloroquine

Sulfasalazine

Leflunomide

Tofacitinib (Xeljanz) (JAKi)

Baricitinib (Olumiant) (JAKi)

My Hand is Swollen Like Bobba Tea

methotrexate brand

Trexall

Methotrexate dosage form

Trexall = oral tablet

SC auto-injector available (Otrexup, Rasuvo) Thigh or abdomen only

Methotrexate

BBW (4):

Monitoring:

BBW: Hepatotoxicity, myelosuppression, mucositis/stomatitis, pregnancy

Monitor: CBC, LFT, CXR, HepB/C (if at risk)

What should be given with MTX

Folate to reduce toxicities

Hydroxychloroquine

brand?

Plaquenil

Hydroxychloroquine

Warning:

Irreversible retinopathy

Sulfasalazine

CI:

Strange AE:

Sulfa allergy

Yellow-orange coloration of skin/urine

Leflunomide brand

Arava

Leflunomide

BBW (2):

Do not use in pregnancy

Hepatotoxicity

Accelerated drug elimination can be given for patients taking which DMARD?

What are the elimination options?

Leflunomide

Cholestyramine

Activated charcoal suspension

In order to start leflunomide, what criteria must be met?

Negative pregnancy test

2 forms of birth control

(Must wait 2 years after stopping therapy to conceive - or use accelerated drug elimination^)

JAK inhibitors

Tofacitinib

Baricitinib

Upadacitinib

JAK inhibitors

BBW (3)

Tofacitinib, Baricitinib, Upadacitinib

- Serious infections including TB

- Malignancy

- Thrombosis

Avoid JAKi with what other meds?

Biologic DMARDs

Methotrexate drug interactions

Do NOT take with alcohol

Decreased renal elimination if NSAID/ASA

Anti-TNF Biologic DMARDs (5)

etanercept (Enbrel) - QW

certolizumab (Cimzia) - Q2W

golimumab (Simponi) - Qmo

adalimumab (Humira) - Q2W

infliximab (Remicade) - IV @week 0,2,6 - q8w

Even Country Girls Are Inflamed

Etanercept

Brand:

Dosing Frequency:

Enbrel

SC weekly dosing

adalimumab

Brand:

Dosing Frequency:

Humira

SQ every other week

Infliximab

Brand:

Dosing:

Notable pearls:

Remicade

IV @week 0,2,6 - then every 8 weeks

Stable only in NS

Delayed hypersensitivity rxn - days after

Infusion Rxn - Premedicate

Certolizumab

Brand:

Dosing frequency:

Cimza

SC every other week

Golimumab

Brand:

Dosing frequency:

Simponi

SC once monthly

IV requires a filter

Which 2 anti-TNF mediations that are typically kept in the fridge can be stored at room temp for up to 14 days?

Etanercept (Enbrel)

Adalimumab (Humira)

Humira should be injected where?

Abdomen or Thigh

Etanercept (Enbrel) should be injected where?

Abdomen

Thigh

Upper arm

Golimumab (Simponi) should be injected where?

Abdomen

Thigh

Upper arm

Anti-TNF biologics

BBW:

Warnings:

Monitoring:

BBW: Serious infections (latent TB reactivation), Malignancies

Warning: Demyelinating disease, HepB reactivation, HF, Hepatotox, Lupus-like syndrome

Monitor: TB, HBV

Non-TNF Biologic DMARDs for RA (5, 1 bolded)

Rituximab (Rituxan)

Anakinra (Kineret)

Abatacept (Orencia)

Tocilizumab (Actemra)

Sarilumab (Kevzara)

Rituxumab

Brand:

Rituxan

_____ must be given with methotrexate (3)

Rituxumab/Ritixin

Inflixumab/Remicaid

Golimumab/Sinmponi

Rituxumab

MOA:

Dosage form

Notable administration pearl

MOA: Depletes CD20 B cells

IV on day 1 and day 15

Premedicate (steroid, antihistamine, APAP)

Rituxumab

BBW:

Infusion-related reactions

HBV reactivation (screen high risk groups)

Methotrexate is dosed _______ for RA and psoriasis

weekly (whereas cancers are higher doses more frequently/daily)

LUPUS

systemic lupus erythematosus (SLE)

Most common in:

Young women of African-American or Asian descent

What condition causes a presentation similar to lupus but is not autoimmune-mediates?

DILE - Drug-Induced Lupus erythematosus

(Usually resolves after drug discontinuation)

Medications that can cause DILE

Methimazole

PTU

Methyldopa

Minocycline

Procainamide

Hydralazine

Anti-TNFi

Terbanafine

Isoniazid

Quinidine

My Pretty Malar Marking Probably Has A TransIent Quality

Symptoms of Lupus (SLE)

Fatigue, Depression, anorexia, weight loss, muscle pain

Malar (facial) rash (butterfly), photosensitivity

Joint pain and stiffness

While _____ and ______ are the most common manifestations of SLE, it can also cause inflammation in other organs such as:

Most common: Arthritis, cutaneous (butterfly rash)

Renal, hematologic, neurologic manifestations

Lupus nephritis kidney disease develops in >50% of Lupus patients

(not a question, blank)

ok

Laboratory findings of Lupus

Positive Antinuclear antibodies (ANA)

Positive anti-single stranded DNA (anti-ssDNA)

Positive anti-double stranded DNA (anti-dsDNA)

Lifestyle change to protect those with Lupus

sunscreen!

Treatment of Lupus often NSAID + PPI but many patients will require an immunosuppressant to control their disease.

Name the common meds for chronic therapy (5)

Hydroxychloroquine

Cyclophosphamide

Azathioprine

Mycophenylate mofetil

Cyclosporine

CC HAM

In some cases, it may take up to __________ to see maximal benefit from treatment of lupus

up to 6 months

There is another drug class for treatment of lupus targeting __cells

What is the drug and BBW

B cells (IgG1-lambda mAb)

Belimumab (Benlysta)

BBW: infections, not w biologics

Calcineurin inhibitor for Lupus

Voclosporin (Lupkynis)

BBW: infection, malignancy

Warning: Nephrotoxic, HTN

AE: HTN, diarrhea, HA, renal impairment

MULTIPLE SCLEROSIS

...

Symptoms of multiple sclerosis

Fatigue

Numbness

Blurred vision

Over time: Deterioration of - cognitive function, muscle spasms, pain, incontinence, gait instability

Diagnosis of multiple sclerosis

MRI

_______________ formulations and _________________ are parenteral drugs that have been the mainstay of multiple sclerosis treatment

Interferon beta formulations

Glatiramer acetate (Copaxone)

Pegylated interferon beta (Brand?) allows for more convenient dosing that is given _________

Plegridy

SQ injection every 14 days

Which agent is preferred during pregnancy?

Glatiramer acetate (Copaxone)

________ and _________ were the first oral medications approved for the treatment of MS

Fingolimod (Gilenya)

Teriflunomide (Aubagio)

Glaterimer Acetate

Brand:

Very general MOA:

Dosing frequency:

Copaxone

MOA: Immune modulator

SC QD or 3x/week

Glaterimer Acetate

warning (1):

AE: (4)

Warning: Chest pain

AE: Inj site rxn, flushing, diaphoresis, dyspnia

Interferon beta products (3)

Interferon beta-1a (Avenox)

Interferon beta-1b (Betaseron, Extavia)

Peginterferon beta-1a (Plegridy)

Interferon beta products: Frequency of dosing

(for each of the 3 agents)

Interferon beta-1a (Avenox = IM weekly, Rebif = SC 3x/wk)

Interferon beta-1b (Betaseron, Extavia) = SC QOD

Peginterferon beta-1a (Plegridy) Q 14d

Interferon beta products:

Warning (4):

AE (1):

Warning: Psychiatric disorders, inj site necrosis, Inc LFT, thyroid dysfunction (Hypo/hyper)

AE: Flu-like sx

Counseling point for administration of interferon beta injections

Do not expel the air bubble in the syringe

Pyrimidine synthesis inhibitor (1)

Band/generic

CI (1)

Teriflunomide (Aubagio)

CI in pregnancy (teratogenicity)

sphingosine 1-phosphate (S1P) receptor modulator

(4) brand/generic

Fingolimod (Gilenya)

Ozanimod (Zeposia)

Ponesidmod (Ponvory)

Siponimod (Mayzent)

sphingosine 1-phosphate (S1P) receptor modulator

CI (2)

Warning/monitoring

CI: MAOi, CYP2C9 3/ 3 genotype (testing required before use)

Warning: Slow HR (monitor x6h after 1st dose, Baseline EKG required)

Macular edema, increase risk of infection (monitor CBC), LFTs

MS can become worse when with therapy is stopped?

sphingosine 1-phosphate (S1P) receptor modulator

Nuclear factor (erythroid-derived 2)-like 2 activators (Nrf2)

(2) brand/generic

Counseling point (1)

Dimethyl fumarate (Tecfidera)

Diroximel fumarate (Vumerity)

Do not crush/chew or sprinkle contents on food