Systemic Steroids and Autoimmune Conditions Flashcards
List eight (8) systemic steroids in order from least potent to most potent, and also indicate their dose equivalent dose, and also indicate which drug has equal mineralocorticoid and glucocorticoid activity (Hint: Cute Hot Pharmacists and Physicians Marry Together and Deliver Babies [CHPPMTDB]
- cortisone (25 mg) [short-acting]
- hydrocortisone (20 mg)** equal mineralo/gluco [short-acting]
- prednisone (5 mg) has SOME mineralo [intermediate-acting]
- prednisolone (5 mg)* some mineralo [intermediate-acting]
- methylprednisolone (4 mg)* some mineralo [intermediate-acting]
- triamcinolone (4 mg) negligible [intermediate-acting]
- dexamethasone (0.75 mg) negligible [long-acting and highest potency]
- betamethasone (0.6 mg) negligible [long-acting and highest potency]
What is definition of immunosuppressed from systemic steroids? How to taper?
A patient is immunosuppressed when using >2mg/kg/day or >20 mg/day of prednisone or prednisone equivalent for > 2 weeks
Reduce dose by 10-20% every few days for 7-14 days.
List seven (7) systemic autoimmune conditions (Hint: R,L,M, R, C, S, P)
- Rheumatoid arthritis
- Systemic Lupus Erythematosus
- Multiple Sclerosis
- Raynaud’s Phenomenon
- Celiac Disease
- Sjogren’s Syndrome
- Psoriasis
List ten (10) drugs that can cause drug-induced lupus erythematosus (DILE) [Hint: My Press Pony Miss Muffin The Queen Is A Terrific Horse MPPMMTQIATH)
- Methimazole
- Procainamide
- Propylthiouracil
- Methyldopa
- Minocycline
- Quinidine
- Isoniazid
- Anti-TNF agents
- Terbinafine
- Hydralazine (alone, and in BiDil)
List three groups of drugs that can cause or worsen Raynaud’s syndrome (hint: CV, chemo, Neuro)
- Beta blockers
- Bleomycin, cisplatin
- Amphetamines, Pseudoephedrine, Cocaine
List eight (8) glucocorticoids
- Cortisone
- Betamethasone (Celestone Soluspan, ReadySharp Betamethasone)
- Dexamethasone (DexPak 6, 10 or 13 day, Decadron, Dexamethasone Intensol, DoubleDex)
- Hydrocortisone (Solu-Cortef, Cortef)
- Methylprednisolone (Medrol, Medrol Therapy Pack, Solu-medrol, Depo-Medrol)
- Prednisone (Prednisone Intensol, Deltasone, Rayos)
- Prednisolone (Millipred, Orapred ODT, Veripred)
- Triamcinolone (Kenalog)
Which glucocorticoids are available PO only? (hint: 3)
- Cortisone
- Prednisolone
- Prednisone
List four (4) serious risks of strong immunosuppressants
- Re-activation of tuberculosis and Hepatitis B and C
- Viruses, if the virus can be prevented by a live vaccine, give vaccine prior to immunosuppressive treatment
- lymphomas and certain skin cancers
- infections
List three (3) differences in clinical presentation between RA and OA
- RA is bilateral and symmetrical
- worse after rest, morning stiffness
- lab: anti-citrullinated peptide antibody (ACPA) and rheumatoid factor (RF)
What is the preferred initial therapy for patients with symptomatic RA treated with a DMARD?
methotrexate
List six (6) Traditional (non-Biologic) Disease-Modifying Antirheumatic Drugs (DMARDs)
- Methotrexate (Otrexup, Rasuvo, Trexall, Xatmep) [
- Hydroxychloroquine (Plaquenil)
- Sulfasalazine (Azulfidine, Azulfidine EN-tabs)
- Leflunomide (Arava)
- Tofacitinib (Xeljanz, Xeljanz XR)
- Baricitinib (Olumiant)
MOA of Otrexup, Rasuvo, Trexall, Xatmep?
Irreversibly binds and inhibits dihydrofolate reductase, inhibiting folate, thymidylate synthease and purine; has immune modulator and anti-inflammatory activity
MOA of Plaquenil?
Not precisely known, immune modulator. Hydrochloroquine
MOA of Azulfidine?
Not precisely known, immune modulator. Sulfasalazine
MOA of Arava?
Inhibits pyrimidine synthesis resulting in anti-proliferative and anti-inflammatory effects. Leflunomide
MOA of Xeljanz?
Inhibits Janus Kinase (JAK) enzymes, which stimulate immune cell function
MOA of Olumiant?
Inhibits Janus Kinase (JAK) enzymes, which stimulate immune cell function
List five (5) Anti-TNF biologic DMARDs?
- Etanercept (Enbrel) weekly SC
- Adalimumab (Humira) QOweek SC (weekly w/o MTX)
- Infliximab (Remicade) (infusion 0, 2, 6 week then q8wk)
- Certolizumab pegol (Cimzia) SC 0, 2, 6 week then QOweek (or 400 mg every 4 weeks)
- Golimumab (Simponi Aria, Simponi) (monthly SC, weeks 0, 4 then q8week IV infusion)
List five (5) other biologic DMARDs (non-TNF inhibitors)
- Rituximab (Rituxan) (IV infusion day 1 and 15 with MTX)
- Anakinra (Kineret) (SC same time each day)
- Abatacept (Orencia) (SC weekly, infusion 0, 2, 4 then q4week)
- Tocilizumab (Actemra) (SC every other week, can increase to weekly. Infusion every 4 weeks)
- Sarilumab (Kevzara) (SC every 2 weeks)
MOA of Rituxan?
Depletes CD20 B cells believed to have a role in RA development and progression. Rituximab
MOA of Kineret?
IL-1 receptor antagonist; IL-1 mediates immunologic reactions in RA; not recommended first line per guidelines
MOA of Orencia?
Inhibits T-cell activation by binding to CD80 and CD86 on antigen presenting cells (blocking interaction with CD28)
MOA of Actemra?
IL-6 receptor antagonist; IL-6 mediates immunologic reactions in RA
MOA of Kevzara?
IL-6 receptor antagonist
List eight (8) common symptoms of SLE
- Fatigue
- Depression
- Anorexia
- Weight loss
- Butterfly rash (Malar rash)
- Muscle pain
- Photosensitivty
- Joint pain and stiffness
What symptoms of SLE contribute greatest to morbidity and mortality? (hint: 3 organ systems)
- Lupus nephritis
- Hematologic (e.g. anemia)
- Neurologic
truthfully there are many more
List five (5) drugs clasically used to treat SLE
- Hydroxychloroquine (FDA label)
- Cyclophosphamide
- Azathioprine
- Mycophenolate mofetil
- Cyclosporine
List a biologic used in treatment of SLE
- Belimumab (Benlysta) (IV infusion every 2 weeks x 3 doses, then every 4 weeks. SC weekly)
MOA of Belysta?
IgG1-lambda monoclonal antibody: prevents the survival of B lymphocytes by blocking the binding of soluble human B lymphocyte stimulator protein (BLyS) to receptors on B lymphocytes; this reduces the activity of B-cell mediated immunity and the autoimmune response
List nine (9) classes of drugs approved for use in MS (hint: 1 chemo, 2 HPA-related drugs, interferons, glatiramer acetate, three oral immunomodulators, 1 related to nerve signal conduction, 1 biologic, 2 human biologic)
- Mitoxantrone (Novantrone)
- Steroids
- Corticotropin (HP Acthar); also called ACTH
- Interferon beta formulations
- Glatiramer acetate
- Oral immunomodulators
- Potassium channel blockers
- Monoclonal antibodies
- Recombinant humanized monoclonal antibodies
What two (2) drug classes have historically been the mainstay of treatment for patients with relapsing forms of MS?
- Interferon beta formulations (Betaseron, Avonex, Rebif, Extavia, Plegridy)
- Glatiramer acetate (Copaxone, Glatopa)
MOA of glatiramer acetate?
Glatiramer acetate (Copaxone) is an immune modulator thought to induce and activate T-lymphocyte suppressor cells in relapsing forms of MS, although the exact mechanism if not well-defined
MOA of interferon beta products?
Interferon beta products alter the expression and response to surface antigens, enhancing immune cell function, although the exact mechanism in MS is not well-defined
List three interferon chemical entities used in interferon beta products for MS?
- inteferon beta-1a
- interferon beta-1b
- peginterferon beta-1a
List two (2) interferon beta-1a products and their routes of administration
- Avonex: IM
2. Rebif: SC
List two (2) interferon beta-1b products and their routes of administration
- Betaseron: SC
2. Extavia: SC
List one (1) peginterferon beta-1a products and their routes of administration
- Plegridy: SC
List three (3) oral immunomodulators approved for MS
- Teriflunomide (Aubagio)
- Fingolimod (Gilenya)
- Dimethyl fumarate (Tecfidera)
MOA of Aubagio?
Active metabolite of leflunomide
MOA of Gilenya
sphingosine 1-receptor modulator. The exact mechanism of action of fingolimod in patients with multiple sclerosis is unknown; however, it may work by reducing lymphocyte migration to the central nervous system
MOA of Tecfidera
NrF2 activator
List one (1) potassium channel blocker that may increase nerve signal conduction and is indicated to improve walking
- Dalfampridine (Ampyra)
List one (1) monoclonal antibody approved for MS
- Natalizumab (Tysabri)
MOA of Tysabri?
monoclonal antibody that bidns to the alpha-4 subunit of integrins expressed on the surface of leukocytes
List two (2) recombinant humanized monoclonal antibodies approved for MS?
- Alemtuzumab (Lemtrada)
2. Ocrelizumab (Ocrevus)
MOA of Lemtrada?
CD52-directed cytolytic monoclonal antibody
MOA of Ocrevus?
Targets CD20+ B cells
List twelve (12) symptoms of MS and corresponding palliative medications
- Incontinence - anticholinergics
- Constipation - laxatives
- Diarrhea - loperamide
- Muscle spasms - Muscle relaxants
- Pain - analgesics
- Localized pain - Botox
- Tremor - propranolol
- depression - SSRI, SNRI if neuropathic pain as well
- fatigue - modafinil, stimulants
- Dizziness, vertigo - meclizine, scopolamine
- cognitive function - acetylcholinesterase inhibitors (donepezil)
- erectile dysfunction - PDE-5
List two symptoms and three complications of Sjogren’s Syndrome
- dry mouth
- dry eyes
- dental caries
- corneal ulceration
- chronic oral infections
In addition to OTC artificial tear drops, what are two topical medications which are approved for dry eyes treatment?
- Cyclosporine emulsion (restasis)
2. Lifitegrast (Xiidra)
List two (2) drugs that are used for dry mouth treatment in patients with Sjgoren’s syndrome
muscarinic agonists:
- Pilocarpine (salagen)
- Cevimeline (Evoxac)
List six (6) topical drug/drug classes for psoriasis
- Steroids
- Retinoids (Tazarotene [Tazorac])
- Coal tar [DHS Tar, Psoriasin, Pentrax Gold]… also in combination with salicylic acid [Tarsum, X-Seb T]
- anthralin [Zithranol, Dritho-Creme HP]
- vitamin D analogs (calcipotriene [Dovonex, Calcitrene]… plus betamethasone (Taclonex ointment, Taclonex salp suspension, Enstilar)
- Topical calcineurin inhibitors (Protopic, Elidel)
List three (3) drug/drug classes for systemic psoriasis treatment
- Retinoids
- Phosphodiesterase-4 inhibitors
- Interleukin receptor antagonists
List 1 retinoid used for systemic psoriasis treatment
- Acitretin (Soriatane)
List 1 phosphodiesterase-4 inhibitor for systemic psoriasis treatment
- Apremilast (Otezla)
List six (6) interleukin receptor antagonists for systemic psoriasis treatment
- Brodalumab (Siliq)
- Guselkumab (Tremfya)
- Ixekizumab (Taltz)
- Secukinumab (Cosentyx)
- Tildrakizumab-asmn (Ilumya)
- Ustekinumab (Stelara)
List three (3) steroid-induced medical conditions (e.g. consequence of short-term side effects mimic medical condition)
- Increase blood glucose -> diabetes
- Increase BP -> HTN
- Increase IOP -> Glaucoma
List two (2) contraindications to systemic steroids
- Live vaccines
2. Serious systemic infections
List eleven (11) side effects of Long-term glucocorticoid use, e.g. Cushing’s Syndrome (G, F, S, W, ID, Psy, Derm, GI, Blood sugar, Gyn, osteo)
- Glaucoma, cataracts
- Fat deposits in face, abdomen, upper back, buffalo hump
- Pink-purple stretch marks (striae) on abdomen, thighs, breasts and arms, thin skin that bruises easily
- Growth retardation, muscle wasting (thin arms and legs relative to rest of body)
- Infection, impaired wound healing
- Psychiatric changes
- Acne
- GI bleeding/esophagitis/ulcers
- Diabetes
- Hirsutism, irregular menstrual periods
- Poor bone health
List three (3) miscellaneous notes about systemic glucocorticoids
- cortisone is a prodrug of cortisol
- prednisone is a prodrug of prednisolone
- prednisolone is used commonly in children, many formulations
List ten (10) risks listed in BBW for methotrexate
- Hepatotoxicity
- Myelosuppression
- Mucositis/stomatitis
- Pregnancy (embryofetal toxicity/fetal death)
- acute renal failure* high dose
- pneumonitis *high dose
- GI toxicity
- dermatologic reactions
- malignant lyphomas
- potentially fatal opportunistic infections
Describe the available formulations of methotrexate (hint: 3 kinds of products)
- single-dose SC autoinjectors: Otrexup, Rasuvo
- oral tablet: Trexall
- Oral solution for peds: Xatmep
List six (6) contraindications to methotrexate
- pregnancy
- breastfeeding
- alcoholism
- chronic liver disease
- blood dyscrasia
- immunodeficiency syndrome
List seven (7) common side effects of methotrexate
- N/V/D (GI)
- Increased LFTs
- Stomatitis
- Alopecia
- Photosensitivity
- arthralgia
- myalgia
List six (6) lab tests that are helpful for monitoring methotrexate side effects
- Baseline: CBC, LFTs + every 2-4 weeks for first 3 months or following dose increase, then 8-12 weeks for 3-6 months, then less frequently
- Chest X-ray
- Hepatitis B and C serologies
- SCr
- PFTs
- TBs
List two (2) miscellaneous notes for methotrexate
- Folate can be given to decrease hematological, GI and hepatic side effects (5 mg PO weekly on the day following MTX administration, some take 1 mg daily on non-MTX day)
- Xatmep requires no preparation: eliminates needs for needles, crushing or splitting, or compounding into an oral solution.
List seven (7) warnings for hydroxychloroquine (hint: 1 most common/classic organ system + others, also rare deficiency warning)
- irreversible retinopathy ***most important
- loss of visual acuity/macular pigment changes
- neuromuscular weakness
- cardiomyopathy
- bone marrow suppression (anemia, leukopenia, thrombocytopenia)
- hypoglycemia
- caution in patients with G6PD deficiency
List seven (7) side effects of Plaquenil
- N/V/D
- abdominal pain
- rash
- pruritus
- headache
- vision changes (Dose-related)
- pigmentation changes of the skin and hair (rare)
List two (2) monitoring consideration of Plaquenil
- eye exam and muscle strength at baseline and every 3 months during prolonged therapy
- CBC and LFTs at baseline and periodically
List three (3) miscellaneous notes of Plaquenil
- lower risk of liver toxicity than MTX, can use as an alternative DMARD in RA when there is a concern for liver disease
- monotherapy; if low disease activity and symptoms <24 months
- If inadequate or no response after 6 months, consider alternative
List three (3) contraindications for Azulfidine
- Patients with a sulfa or salicylate allergy
- GI or GU obstruction
- porphyria
List five (5) warnings for Azulfidine
- Blood dyscrasias
- severe skin reactions (SJS/TEN)
- hepatic failure
- pulmonary fibrosis
- use in caution with G6PD deficiency
List two (2) miscellaneous notes for Azulfidine
- yellow-orange discoloration of skin/urine
2. impairs folate absorption, can give 1 mg/day folate supplement
List two (2) boxed warnings for Arava
- Embryo-fetal toxicity; exclude pregnancy prior to starting therapy
- hepatotoxicity: avoid in pre-existing liver disease or ALT >2x upper limit of normal (ULN)
List three (3) contraindications for Arava
- pregnancy
- severe hepatic impairment
- current teriflunomide therapy
List six (6) warnings for Arava
- severe infections
- serious skin reactions (SJS/TEN)
- peripheral neuropathy
- interstitial lung disease
- hypertension
- upon discontinuation of treatment, use accelerated drug elimination procedure to reduce levels ofa ctive metabolite, otherwise weight >2 years before pregnancy
List six (6) side effects of Arava
- increased LFTs
- nausea
- diarrhea
- respiratory infections
- rash
- headache
List four (4) monitoring considerations for Arava
- LFTs and CBC at baseline and monthly for first 6 months
- BP at baseline and regularly
- screen for TB
- screen for pregnancy
List two drugs used for Arava accelerated drug elimination procedure (e.g. Miscellaneous notes for Arava)
Accelerated drug elimination options:
- cholestyramine 8 grams PO TID x 11 days (use 4 g if 8 g dose is not tolerated)
- activated charcoal suspension 50 g PO Q12H x 11 days
List two (2) boxed warnings for Xeljanz
- serious infections including tuberculosis (TB), fungal, viral, bacterial or opportunistic infections
- malignancy: increased risk for lymphomas and other malignancies
List four (4) precautions/warnings for Xeljanz
- GI perforation
- increased LFTs
- not studied in patients with a baseline CrCl <40 ml/min
- avoid live vaccines
List six (6) side effects of Xeljanz
- upper respiratory tract infections (URTIs)
- urinary tract infections (UTIs)
- diarrhea
- headache
- hypertension
- increased lipids
List five (5) monitoring considerations for Xeljanz
- CBC (for lymphopenia, neutropenia and anemia) baseline then 4-8 weeks later, then every 3 months
- lipids baseline then 4-8 weeks later, then every 3 months
- LFTs (at baseline and periodically thereafter)
- new onset abdominal pain
- signs of infection
List two (2) miscellaneous notes for Xeljanz
- caution in patients of asian descent (increased frequency of side effects)
- available through specialty/network pharmacies
List two (2) boxed warnings for Olumiant that make it different than Xeljanz
- thrombosis
- including DVT/PE and arterial thrombosis
- many were serious and some resulted in death
List one (1) pregnancy consideration for all anti-TNF biologic DMARDs
each drug has its own pregnancy registry due to unknown risks to the fetus
List two (2) boxed warnings for anti-TNF biologic DMARDs
- Serious infections (most common), including TB, fungal, viral, bacterial or opportunistic, screen for latent TB prior to therapy.
- Lymphomas and other malignancies
List three (3) contraindications for anti-TNF biologic DMARDs (1 general, 1 Remicade, 1 Enbrel)
- active systemic infection
- infliximab: doses >5 mg/kg in moderate-severe heart failure
- etanercept: sepsis
List seven (7) warnings of things anti-TNF biologic DMARDs can cause + one (1) warning about therapy selection
- demyelinating disease*
- hepatitis B reactivation *
- heart failure *
- hepatotoxicity *
- lupus-like syndrome *
- seizures
- myelo-suppression and severe infections
- Do not use with other biologic DMARDs or live vaccines
List six (6) side effects of anti-TNF biologic DMARDs (hint: 5 general + 1 humira)
- infections
- injection site reactions (redness, rash, swelling, itching, bruising)
- positive anti-nuclear antibodies
- headache
- nausea
- Humira: increased creatinine phosphokinase (CPK)
List four (4) notes about remicade IV infusions
- requires a filter
- stable in NS only
- infusion reactions: hypotension, fever, chills, pruritus (can premidate with APAP, antihistamine, steroids)
- delayed hypersensitivity reaction: 3-12 days (fever, rash, myalgia, headache, sore throat)