46. Systemic Steroids + Autoimmune Conditions (not completed) Flashcards
Fludocortisone mimics ___. It has mineral corticoid acitivty which is used to maintain a balance of ___. Helps keep BP stable.
Aldosterone
Water and electrolytes
Fludrocortisone is FDA approved for ___ but also used off-label for ___
Addison’s disease
Orthostatic hypotension
Other commonly used steroids (e.g. prednisone, hydrocortisone) have more __ activity which has more anti-inflammatory effects
Glucocorticoid
When are steroids typically used
Inflammatory conditions
Immune suppression post-transplant
Adrenal insufficiency (to replace endogenous steroids that the adrenal gland is not producing enough of)
Systemic steroids can cause the adrenal gland to stop producing ___ d/t feedback inhibition. This is called suppression of the ____
Cortisol
Hypothalamic pituitary-adrenal (HPA) axis
T/F: when long-term steroids are d/c, they can be stopped immediately
False - taper off to give adrenal gland time to resume cortisol production
___ can develop when the adrenal gland produces too much cortisol or if exogenous steroids are taken in doses higher than normal amt of endogenous cortisol
Cushing’s syndrome
____ can be thought of the opposite of Cushing’s syndrome. In this condition, the adrenal gland is not making enough ____. If exogenous steroids are stopped suddenly, it can cause an ____, which can be fatal.
Addison’s disease
cortisol
“Addisonian Crisis”
Ways to reduce systemic steroid risks
Alternate day dosing
Localize: For joint inflammation, Inject into join (localize) // for asthma, use ICS
For condition in the gut, us steroid with low systemic absorption such as budesonide (Entocort EC)
For conditions that require long-term use, use lowest possible dose for shortest possible time
Long-term effects of steroids (e.g. Cushing’s Syndrome)
Psychiatric changes (anxiety, depression ,delirium, psychoses), HA, intracranial HTN, hypothyroidism
Glaucoma, cataracts
Acne
Fat deposits in face (moon face), abdomen, upper back (buffalo hump)
GI bleeding/esophagitis/ulcers
Pink-purple stretch marks (striae) on abdomen, thighs, breasts, and arms, think skin that bruises easily
Diabetes
Growth retardation, muscle wasting (thin arms and legs relative to rest of body)
Poor bone health
infection, impaired wound healing
Women only: hair growth on face/body (hisutism), irregular or absent menstrual periods
Steroids least potent to most potent and dose equivalence
Cute Hot Pharmacists and Physicians Marry Together & Deliver Babies
Cortisone 25mg
Hydrocortisone (Solu-Cortef)20mg
Prednisone (Millipred, Orapred ODT) 5mg
Prednisolone (Deltasone) 5mg
Methylprednisolone (Medrol, Solu-Medrol) 4mg
Triamcinolone (Kenalog) 4mg
Dexamethasone (Decadron) 0.75mg
Betamethasone (Celestone) 0.6mg
Short term side effects of systemic glucocorticoids (<1 month)
Increased appetite/weight gain, emotional instability (euphoria, mood swings, irritability) insomnia, increased intraocular pressure, fluid retention, indigestion, bitter taste, increased BP/BG with higher doses
Cortisone is prodrug of ___
cortisone
Prednisone is prodrug of ___
prednisolone
Methylprednisolone formulations
Therapy pack (Medrol Dose Pack” and injection
Warnings with systemic glucocorticoids
Adrenal suppression - HPA axes suppression may lead to adrenal crisis and death
If taking longer than 14 days, taper
A patient is considered immunosuppressed when using ≥ ____/kg/day or ≥ ____/day of prednisone or equivalent for > 2 weeks
≥2mg/kg/day or ≥20mg/day for > 2 weeks
Medrol Therapy Pack dosing
Tapered dosing with 4mg tabs x 21 over 6 days
Day 1: 2 tabs before breakfast, 1 tab after lunch, 1 tab after dinner, 2 tabs at bedtime
Day 2: 1 tab before breakfast, after lunch, and after dinner, 2 tabs at bedtime
Day 3: 1 tablet before breakfast, after lunch, after dinner, and at bedtime
Day 4: 1 tablet before breakfast, after lunch, and at bedtime
Day 5: 1 tablet before breakfast and at bedtime
Day 6: 1 tablet before breakfast
Common symptoms of most autoimmune diseases include ___
fatigue, weakness, and pain
Nonspecific lab blood tests can be useful in detecting inflammation including ___
erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF) and anti-nuclear antibody (ANA)
The use of strong immunosuppressants can increase the risk of certain conditions including ____
Reactivation of tuberculosis and hep B or C (if present): testing (and treatment, if needed) must be done prior to starting immunosuppressive meds
Viruses: if live vaccine, must be given prior to start
Lymphomas and certain skin cancers: normally suppressed by competent immune system
Infections
Rheumatoid arthritis (RA) is a chronic, progressive autoimmune disorder that primarily affects __. Other organs including kidneys, eyes, heart, and lungs can be affected.
joints
Typical location of Rheumatoid arthritis
Bilateral, symmetrical disease is consistent with RA dx (in contrast to osteoarthritis (OA) which presents unilaterally)
Classic symptoms of rheumatoid arthritis
Joint swelling
pain and stiffness worse after rest (“morning stiffness”, note: OA does not cause prolonged stiffness)
bone deformity
Others: weakness, difficult to move, edema, redness
__ and __ are useful labs in diagnosing RA
Anti-citrullinated peptide antibody (ACPA)
Rheumatoid factor (RF)
Patients with symptomatic RA should be started on ___ regardless of the severity of disease
disease-modifying antirheumatic drug (DMARD)
DMARDs work via various mechanisms to _____
slow disease process and help further joint damage
___ is the preferred initial therapy of most RA patients
Methotrexate (MTX) (Trexall)
Never use 2 biologic DMARDs in combo d/t risk of ___
serious (fatal) infections
Methotrexate dosing
7.5-20mg once weekly (PO, SC, IM) - safer to take as single dose (rather than divided oral dosages of 2.5mg Q12H x3 doses per week)
Never dose daily for RA (liver damage concern)
MOA of methotrexate)
Inhibits dihydrofolate reductase, inhibiting folate
Methotrexate formulations
Oral tab = Trexall
SC Auto-injectors = Otrexup, Rasuvo
Oral solution for ped pts = Xatmep
Boxed warnings for methotrexate
Hepatotoxicity, myelosuppression, mucositis/stomatits, pregnancy
Others: acute renal failure, pneumonitis, GI tox, dermatologic reactions, malignant lymphomas, potentially fatal opportunistic infections
Renal and lung tox more likely when higher oncology doses
Monitoring for Methotrexate
CBC, LFTs, chest X-ray, hep B and C (if at high risk)
Others: SCr, PFTs, TB test
Folate can be given with methotrexate to decrease _____ side effects. Give 5mg po weekly on the day following MTX administration (some take 1mg daily on non-MTX days)
hematological, GI, and hepatic
Hydroxychloroquine (Plaquenil) warnings
Irreversible retinopathy
What Non-biologic DMARDs for RA can cause yellow-orange coloration of skin/urine?
Sulfasalazine
Contraindication for sulfasalazine
Sulfa or salicylate allergy
GI or GU obstruction, porphyria
MOA Leflunomide (Arava)
Inhibits pyrimidine synthesis»_space; anti-proliferative and anti-inflammatory effects
Boxed warning for Leflunomide (Arava)
Do NOT use in pregnancy (teratogenic) - test for prior to starting therapy
Hepatotoxicity - avoid in pre-existing liver disease or ALT >2ULN
Contraindication for Leflunomide (Arava)
Pregnancy
Leflunomide (Arava) pregnancy precautions
Must have neg pregnancy test prior and use 2 forms of birth control during treatment
If pregnancy is desired, must wait 2 years after d/c or accelerated drug elimination procedure
Accelerated drug elimination options for leflunomide (Arava)
- Cholestyramine 8g PO TID x 11 days (use 4g if 8g dose not tolerated)
- Activated charcoal suspension 50mg PO Q12H x 11 days
Boxed warning for Janus Kinase Inhibitors (Tofacitinib (Xeljanz), Baricitinib (Olumiant), Updacitinib (Rinvoq))
Serious infections
Malignancy
Thrombosis
Do NOT use with biologic DMARDs or potent immunosuppressants
Concern with methotrexate with alcohol
Do not take with alcohol, increased risk of liver tox
Concern with methotrexate with NSAIDs/aspirin
Decreased renal elimination of methotrexate»_space; methotrexate toxicity
